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Alvocidib

Alvocidib is a synthetic N-methylpiperidinyl chlorophenyl flavone compound. As an inhibitor of cyclin-dependent kinase, alvocidib induces cell cycle arrest by preventing phosphorylation of cyclin-dependent kinases (CDKs) and by down-regulating cyclin D1 and D3 expression, resulting in G1 cell cycle arrest and apoptosis. This agent is also a competitive inhibitor of adenosine triphosphate activity. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Current developer:   Sanofi-Aventis Inc.

Phase II study of flavopiridol (Alvocidib) with docetaxel in refractory, metastatic pancreatic cancer. Ten patients were enrolled, and 9 were evaluable for response. No objective responses were observed; however, 3 patients (33%) achieved transient stable disease, with one of these patients achieving a 20% reduction in tumor size. Median survival was 4.2 months, with no patients alive at the time of analysis. Adverse events were significant, with 7 patients (78%) requiring >or=1 dose reduction for transaminitis (11%), grade 4 neutropenia (33%), grade 3 fatigue (44%), and grade 3 diarrhea (22%). The combination of flavopiridol and docetaxel has minimal activity and significant toxicity in this patient population. These results reflect the challenges of treating patients with PC in a second-line setting where the risk/benefit equation is tightly balanced. (source: Pancreatology. 2009;9(4):404-9.)

Phase I trial results using Alvoicib to treat patients with recurrent or refractory B-cell neoplasms. Sixteen patients were treated. The MTD was established as 1.3 mg/m(2) for bortezomib and 30 mg/m(2) for alvocidib (both the 30-minute bolus and 4-hour infusions). Common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. Common nonhematologic toxicities included fatigue and febrile neutropenia. DLTs included fatigue, febrile neutropenia, and elevated aspartate aminotransferase (AST) levels. Two complete responses (CR; 12%) and five partial responses (PR; 31%) were observed at the MTD (overall response rate = 44%). Pharmacokinetic results were typical for alvocidib and pharmacodynamic studies yielded variable results. The combination of bortezomib and alvocidib is tolerable and an MTD has been established for the tested schedule. The regimen appears active in patients with relapsed and/or refractory multiple myeloma or non-Hodgkin's lymphoma, justifying phase II studies to determine the activity of this regimen more definitively. (source: Clin Cancer Res. 2011 May 15;17(10):3388-97. ) 

 1: Jones JA, Kraut EH, Deam D, Byrd JC, Grever MR. Hematologic improvement after flavopiridol treatment of pentostatin and rituximab refractory hairy cell leukemia. Leuk Lymphoma. 2011 Dec 13. [Epub ahead of print] PubMed PMID: 22165992.

2: Nelson DM, Joseph B, Hillion J, Segal J, Karp JE, Resar LM. Flavopiridol induces BCL-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia. Leuk Lymphoma. 2011 Oct;52(10):1999-2006. Epub 2011 Jul 5. PubMed PMID: 21728742; PubMed Central PMCID: PMC3214625.

3: Blum KA, Ruppert AS, Woyach JA, Jones JA, Andritsos L, Flynn JM, Rovin B, Villalona-Calero M, Ji J, Phelps M, Johnson AJ, Grever MR, Byrd JC. Risk factors for tumor lysis syndrome in patients with chronic lymphocytic leukemia treated with the cyclin-dependent kinase inhibitor, flavopiridol. Leukemia. 2011 Sep;25(9):1444-51. doi: 10.1038/leu.2011.109. Epub 2011 May 24. PubMed PMID: 21606960; PubMed Central PMCID: PMC3162125.

4: Liu X, Shi S, Lam F, Pepper C, Fischer PM, Wang S. CDKI-71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer cells compared to flavopiridol. Int J Cancer. 2012 Mar 1;130(5):1216-26. doi: 10.1002/ijc.26127. Epub 2011 Jun 21. PubMed PMID: 21484792.

5: Holkova B, Perkins EB, Ramakrishnan V, Tombes MB, Shrader E, Talreja N, Wellons MD, Hogan KT, Roodman GD, Coppola D, Kang L, Dawson J, Stuart RK, Peer C, Figg WD Sr, Kolla S, Doyle A, Wright J, Sullivan DM, Roberts JD, Grant S. Phase I trial of bortezomib (PS-341; NSC 681239) and alvocidib (flavopiridol; NSC 649890) in patients with recurrent or refractory B-cell neoplasms. Clin Cancer Res. 2011 May 15;17(10):3388-97. Epub 2011 Mar 29. PubMed PMID: 21447728; PubMed Central PMCID: PMC3096752.

6: Karp JE, Smith BD, Resar LS, Greer JM, Blackford A, Zhao M, Moton-Nelson D, Alino K, Levis MJ, Gore SD, Joseph B, Carraway H, McDevitt MA, Bagain L, Mackey K, Briel J, Doyle LA, Wright JJ, Rudek MA. Phase 1 and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias. Blood. 2011 Mar 24;117(12):3302-10. Epub 2011 Jan 14. PubMed PMID: 21239698; PubMed Central PMCID: PMC3069672.

7: Haque A, Koide N, Iftakhar-E-Khuda I, Noman AS, Odkhuu E, Badamtseren B, Naiki Y, Komatsu T, Yoshida T, Yokochi T. Flavopiridol inhibits lipopolysaccharide-induced TNF-α production through inactivation of nuclear factor-κB and mitogen-activated protein kinases in the MyD88-dependent pathway. Microbiol Immunol. 2011 Mar;55(3):160-7. doi: 10.1111/j.1348-0421.2010.00304.x. PubMed PMID: 21204955.

8: Song Y, Shen K, Xu F. [Synergism of antitumor effects on ovarian carcinoma using autocatalytic caspase-3 combined with flavopiridol]. Zhonghua Fu Chan Ke Za Zhi. 2010 Oct;45(10):781-6. Chinese. PubMed PMID: 21176562.

9: Huang JM, Sheard MA, Ji L, Sposto R, Keshelava N. Combination of vorinostat and flavopiridol is selectively cytotoxic to multidrug-resistant neuroblastoma cell lines with mutant TP53. Mol Cancer Ther. 2010 Dec;9(12):3289-301. PubMed PMID: 21159612.

10: Wang L, Harshman SW, Liu S, Ren C, Xu H, Sallans L, Grever M, Byrd JC, Marcucci G, Freitas MA. Assaying pharmacodynamic endpoints with targeted therapy: flavopiridol and 17AAG induced dephosphorylation of histone H1.5 in acute myeloid leukemia. Proteomics. 2010 Dec;10(23):4281-92. PubMed PMID: 21110323; PubMed Central PMCID: PMC3021470.

11: Cimica V, Smith ME, Zhang Z, Mathur D, Mani S, Kalpana GV. Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen. BMC Cancer. 2010 Nov 19;10:634. PubMed PMID: 21092078; PubMed Central PMCID: PMC2998513.

12: Schmerwitz UK, Sass G, Khandoga AG, Joore J, Mayer BA, Berberich N, Totzke F, Krombach F, Tiegs G, Zahler S, Vollmar AM, Fürst R. Flavopiridol protects against inflammation by attenuating leukocyte-endothelial interaction via inhibition of cyclin-dependent kinase 9. Arterioscler Thromb Vasc Biol. 2011 Feb;31(2):280-8. Epub 2010 Nov 18. PubMed PMID: 21088252.

13: Ni W, Ji J, Dai Z, Papp A, Johnson AJ, Ahn S, Farley KL, Lin TS, Dalton JT, Li X, Jarjoura D, Byrd JC, Sadee W, Grever MR, Phelps MA. Flavopiridol pharmacogenetics: clinical and functional evidence for the role of SLCO1B1/OATP1B1 in flavopiridol disposition. PLoS One. 2010 Nov 1;5(11):e13792. PubMed PMID: 21072184; PubMed Central PMCID: PMC2967470.

14: Wang LM, Ren DM. Flavopiridol, the first cyclin-dependent kinase inhibitor: recent advances in combination chemotherapy. Mini Rev Med Chem. 2010 Oct;10(11):1058-70. Review. PubMed PMID: 21047304.

15: Myatt D, Johnson L, Baumli S, Siligardi G. The binding of flavopiridol to blood serum albumin. Chirality. 2010;22 Suppl 1:E40-3. PubMed PMID: 21038395.

16: Dickson MA, Shah MA, Rathkopf D, Tse A, Carvajal RD, Wu N, Lefkowitz RA, Gonen M, Cane LM, Dials HJ, Schwartz GK. A phase I clinical trial of FOLFIRI in combination with the pan-cyclin-dependent kinase (CDK) inhibitor flavopiridol. Cancer Chemother Pharmacol. 2010 Nov;66(6):1113-21. Epub 2010 Feb 21. PubMed PMID: 20953860; PubMed Central PMCID: PMC2957673.

17: Ramaswamy B, Phelps MA, Baiocchi R, Bekaii-Saab T, Ni W, Lai JP, Wolfson A, Lustberg ME, Wei L, Wilkins D, Campbell A, Arbogast D, Doyle A, Byrd JC, Grever MR, Shah MH. A dose-finding, pharmacokinetic and pharmacodynamic study of a novel schedule of flavopiridol in patients with advanced solid tumors. Invest New Drugs. 2010 Oct 12. [Epub ahead of print] PubMed PMID: 20938713.

18: Dickson MA, Rathkopf DE, Carvajal RD, Grant S, Roberts JD, Reid JM, Ames MM, McGovern RM, Lefkowitz RA, Gonen M, Cane LM, Dials HJ, Schwartz GK. A phase I pharmacokinetic study of pulse-dose vorinostat with flavopiridol in solid tumors. Invest New Drugs. 2011 Oct;29(5):1004-12. Epub 2010 May 12. PubMed PMID: 20461440.

19: Blum W, Phelps MA, Klisovic RB, Rozewski DM, Ni W, Albanese KA, Rovin B, Kefauver C, Devine SM, Lucas DM, Johnson A, Schaaf LJ, Byrd JC, Marcucci G, Grever MR. Phase I clinical and pharmacokinetic study of a novel schedule of flavopiridol in relapsed or refractory acute leukemias. Haematologica. 2010 Jul;95(7):1098-105. Epub 2010 May 11. PubMed PMID: 20460644; PubMed Central PMCID: PMC2895033.

20: van der Jagt RH. Sequential flavopiridol, mitoxantrone and cytosine arabinoside for newly diagnosed poor risk acute myeloid leukemia. What to do next? Leuk Res. 2010 Jul;34(7):856-7. Epub 2010 Apr 7. PubMed PMID: 20378170.

21: Kodaira H, Kusuhara H, Ushiki J, Fuse E, Sugiyama Y. Kinetic analysis of the cooperation of P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp/Abcg2) in limiting the brain and testis penetration of erlotinib, flavopiridol, and mitoxantrone. J Pharmacol Exp Ther. 2010 Jun;333(3):788-96. Epub 2010 Mar 19. PubMed PMID: 20304939.

22: Bright SA, Campiani G, Deininger MW, Lawler M, Williams DC, Zisterer DM. Sequential treatment with flavopiridol synergistically enhances pyrrolo-1,5-benzoxazepine-induced apoptosis in human chronic myeloid leukaemia cells including those resistant to imatinib treatment. Biochem Pharmacol. 2010 Jul 1;80(1):31-8. Epub 2010 Mar 3. PubMed PMID: 20206141.

23: Nitta N, Sonoda A, Seko A, Ohta S, Nagatani Y, Tsuchiya K, Otani H, Tanaka T, Kanasaki S, Takahashi M, Murata K. A combination of cisplatin-eluting gelatin microspheres and flavopiridol enhances anti-tumour effects in a rabbit VX2 liver tumour model. Br J Radiol. 2010 May;83(989):428-32. Epub 2009 Dec 17. PubMed PMID: 20019172.

24: Lin TS, Blum KA, Fischer DB, Mitchell SM, Ruppert AS, Porcu P, Kraut EH, Baiocchi RA, Moran ME, Johnson AJ, Schaaf LJ, Grever MR, Byrd JC. Flavopiridol, fludarabine, and rituximab in mantle cell lymphoma and indolent B-cell lymphoproliferative disorders. J Clin Oncol. 2010 Jan 20;28(3):418-23. Epub 2009 Dec 14. PubMed PMID: 20008633; PubMed Central PMCID: PMC2815704.

25: Karp JE, Blackford A, Smith BD, Alino K, Seung AH, Bolaños-Meade J, Greer JM, Carraway HE, Gore SD, Jones RJ, Levis MJ, McDevitt MA, Doyle LA, Wright JJ. Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Leuk Res. 2010 Jul;34(7):877-82. Epub 2009 Dec 4. PubMed PMID: 19962759; PubMed Central PMCID: PMC2875369.

26: Rathkopf D, Dickson MA, Feldman DR, Carvajal RD, Shah MA, Wu N, Lefkowitz R, Gonen M, Cane LM, Dials HJ, Winkelmann JL, Bosl GJ, Schwartz GK. Phase I study of flavopiridol with oxaliplatin and fluorouracil/leucovorin in advanced solid tumors. Clin Cancer Res. 2009 Dec 1;15(23):7405-11. Epub 2009 Nov 24. PubMed PMID: 19934304; PubMed Central PMCID: PMC2787644.

27: Fekrazad HM, Verschraegen CF, Royce M, Smith HO, Chyi Lee F, Rabinowitz I. A phase I study of flavopiridol in combination with gemcitabine and irinotecan in patients with metastatic cancer. Am J Clin Oncol. 2010 Aug;33(4):393-7. PubMed PMID: 19884803.

28: Lin TS, Ruppert AS, Johnson AJ, Fischer B, Heerema NA, Andritsos LA, Blum KA, Flynn JM, Jones JA, Hu W, Moran ME, Mitchell SM, Smith LL, Wagner AJ, Raymond CA, Schaaf LJ, Phelps MA, Villalona-Calero MA, Grever MR, Byrd JC. Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J Clin Oncol. 2009 Dec 10;27(35):6012-8. Epub 2009 Oct 13. PubMed PMID: 19826119; PubMed Central PMCID: PMC2793044.

29: Christian BA, Grever MR, Byrd JC, Lin TS. Flavopiridol in chronic lymphocytic leukemia: a concise review. Clin Lymphoma Myeloma. 2009;9 Suppl 3:S179-85. Review. PubMed PMID: 19778838.

30: Ali A, Ghosh A, Nathans RS, Sharova N, O'Brien S, Cao H, Stevenson M, Rana TM. Identification of flavopiridol analogues that selectively inhibit positive transcription elongation factor (P-TEFb) and block HIV-1 replication. Chembiochem. 2009 Aug 17;10(12):2072-80. PubMed PMID: 19603446; PubMed Central PMCID: PMC2754223.

31: Purcell EK, Thompson DE, Ludwig KA, Kipke DR. Flavopiridol reduces the impedance of neural prostheses in vivo without affecting recording quality. J Neurosci Methods. 2009 Oct 15;183(2):149-57. Epub 2009 Jun 26. PubMed PMID: 19560490.

32: Bonvini P, Zorzi E, Mussolin L, Monaco G, Pigazzi M, Basso G, Rosolen A. The effect of the cyclin-dependent kinase inhibitor flavopiridol on anaplastic large cell lymphoma cells and relationship with NPM-ALK kinase expression and activity. Haematologica. 2009 Jul;94(7):944-55. Epub 2009 Jun 16. PubMed PMID: 19535344; PubMed Central PMCID: PMC2704305.

33: Carvajal RD, Tse A, Shah MA, Lefkowitz RA, Gonen M, Gilman-Rosen L, Kortmansky J, Kelsen DP, Schwartz GK, O'Reilly EM. A phase II study of flavopiridol (Alvocidib) in combination with docetaxel in refractory, metastatic pancreatic cancer. Pancreatology. 2009;9(4):404-9. Epub 2009 May 19. PubMed PMID: 19451750.

34: Zhou L, Schmidt K, Nelson FR, Zelesky V, Troutman MD, Feng B. The effect of breast cancer resistance protein and P-glycoprotein on the brain penetration of flavopiridol, imatinib mesylate (Gleevec), prazosin, and 2-methoxy-3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)propanoic acid (PF-407288) in mice. Drug Metab Dispos. 2009 May;37(5):946-55. Epub 2009 Feb 18. PubMed PMID: 19225039.

35: Budak-Alpdogan T, Chen B, Warrier A, Medina DJ, Moore D, Bertino JR. Retinoblastoma tumor suppressor gene expression determines the response to sequential flavopiridol and doxorubicin treatment in small-cell lung carcinoma. Clin Cancer Res. 2009 Feb 15;15(4):1232-40. Epub 2009 Jan 27. PubMed PMID: 19174488.

36: Phelps MA, Lin TS, Johnson AJ, Hurh E, Rozewski DM, Farley KL, Wu D, Blum KA, Fischer B, Mitchell SM, Moran ME, Brooker-McEldowney M, Heerema NA, Jarjoura D, Schaaf LJ, Byrd JC, Grever MR, Dalton JT. Clinical response and pharmacokinetics from a phase 1 study of an active dosing schedule of flavopiridol in relapsed chronic lymphocytic leukemia. Blood. 2009 Mar 19;113(12):2637-45. Epub 2008 Nov 3. PubMed PMID: 18981292; PubMed Central PMCID: PMC2661854.

37: Zaher M, Akrout I, Mirshahi M, Kolb JP, Billard C. Noxa upregulation is associated with apoptosis of chronic lymphocytic leukemia cells induced by hyperforin but not flavopiridol. Leukemia. 2009 Mar;23(3):594-6. Epub 2008 Sep 11. PubMed PMID: 18784742.

38: Yang X, Zhao X, Phelps MA, Piao L, Rozewski DM, Liu Q, Lee LJ, Marcucci G, Grever MR, Byrd JC, Dalton JT, Lee RJ. A novel liposomal formulation of flavopiridol. Int J Pharm. 2009 Jan 5;365(1-2):170-4. Epub 2008 Aug 20. PubMed PMID: 18778761; PubMed Central PMCID: PMC3035394.

39: Liu Q, Farley KL, Johnson AJ, Muthusamy N, Hofmeister CC, Blum KA, Schaaf LJ, Grever MR, Byrd JC, Dalton JT, Phelps MA. Development and validation of a highly sensitive liquid chromatography/mass spectrometry method for simultaneous quantification of lenalidomide and flavopiridol in human plasma. Ther Drug Monit. 2008 Oct;30(5):620-7. PubMed PMID: 18708993.

40: Hara T, Omura-Minamisawa M, Kang Y, Cheng C, Inoue T. Flavopiridol potentiates the cytotoxic effects of radiation in radioresistant tumor cells in which p53 is mutated or Bcl-2 is overexpressed. Int J Radiat Oncol Biol Phys. 2008 Aug 1;71(5):1485-95. PubMed PMID: 18640498.

41: George S, Kasimis BS, Cogswell J, Schwarzenberger P, Shapiro GI, Fidias P, Bukowski RM. Phase I study of flavopiridol in combination with Paclitaxel and Carboplatin in patients with non-small-cell lung cancer. Clin Lung Cancer. 2008 May;9(3):160-5. PubMed PMID: 18621626.

42: Baumli S, Lolli G, Lowe ED, Troiani S, Rusconi L, Bullock AN, Debreczeni JE, Knapp S, Johnson LN. The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation. EMBO J. 2008 Jul 9;27(13):1907-18. Epub 2008 Jun 19. PubMed PMID: 18566585; PubMed Central PMCID: PMC2486423.

43: Ge Y, Byun JS, De Luca P, Gueron G, Yabe IM, Sadiq-Ali SG, Figg WD, Quintero J, Haggerty CM, Li QQ, De Siervi A, Gardner K. Combinatorial antileukemic disruption of oxidative homeostasis and mitochondrial stability by the redox reactive thalidomide 2-(2,4-difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione (CPS49) and flavopiridol. Mol Pharmacol. 2008 Sep;74(3):872-83. Epub 2008 Jun 12. PubMed PMID: 18556456; PubMed Central PMCID: PMC2778846.

44: Phelps MA, Rozewski DM, Johnston JS, Farley KL, Albanese KA, Byrd JC, Lin TS, Grever MR, Dalton JT. Development and validation of a sensitive liquid chromatography/mass spectrometry method for quantitation of flavopiridol in plasma enables accurate estimation of pharmacokinetic parameters with a clinically active dosing schedule. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jun 1;868(1-2):110-5. Epub 2008 Apr 22. PubMed PMID: 18490204; PubMed Central PMCID: PMC2504738.

45: Zvelebil MJ. Flavopiridol Hoechst AG. IDrugs. 1998 Jun;1(2):241-6. PubMed PMID: 18465538.

46: Ambrosini G, Seelman SL, Qin LX, Schwartz GK. The cyclin-dependent kinase inhibitor flavopiridol potentiates the effects of topoisomerase I poisons by suppressing Rad51 expression in a p53-dependent manner. Cancer Res. 2008 Apr 1;68(7):2312-20. PubMed PMID: 18381438.

47: Song Y, Shen K, Tang PP. [Therapeutic effect of flavopiridol, a small molecular cyclin-dependent kinase inhibitor, in human ovarian carcinoma]. Zhonghua Fu Chan Ke Za Zhi. 2007 Nov;42(11):761-4. Chinese. PubMed PMID: 18307904.

48: Takada Y, Sethi G, Sung B, Aggarwal BB. Flavopiridol suppresses tumor necrosis factor-induced activation of activator protein-1, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK), p44/p42 MAPK, and Akt, inhibits expression of antiapoptotic gene products, and enhances apoptosis through cytochrome c release and caspase activation in human myeloid cells. Mol Pharmacol. 2008 May;73(5):1549-57. Epub 2008 Feb 20. PubMed PMID: 18287248.

49: Smith ME, Cimica V, Chinni S, Challagulla K, Mani S, Kalpana GV. Rhabdoid tumor growth is inhibited by flavopiridol. Clin Cancer Res. 2008 Jan 15;14(2):523-32. PubMed PMID: 18223228.

50: Iyirhiaro GO, Brust TB, Rashidian J, Galehdar Z, Osman A, Phillips M, Slack RS, Macvicar BA, Park DS. Delayed combinatorial treatment with flavopiridol and minocycline provides longer term protection for neuronal soma but not dendrites following global ischemia. J Neurochem. 2008 May;105(3):703-13. Epub 2008 Jan 17. PubMed PMID: 18205749.

51: Hussain SR, Lucas DM, Johnson AJ, Lin TS, Bakaletz AP, Dang VX, Viatchenko-Karpinski S, Ruppert AS, Byrd JC, Kuppusamy P, Crouser ED, Grever MR. Flavopiridol causes early mitochondrial damage in chronic lymphocytic leukemia cells with impaired oxygen consumption and mobilization of intracellular calcium. Blood. 2008 Mar 15;111(6):3190-9. Epub 2008 Jan 11. PubMed PMID: 18192508; PubMed Central PMCID: PMC2265456.

52: Mitchell C, Park MA, Zhang G, Yacoub A, Curiel DT, Fisher PB, Roberts JD, Grant S, Dent P. Extrinsic pathway- and cathepsin-dependent induction of mitochondrial dysfunction are essential for synergistic flavopiridol and vorinostat lethality in breast cancer cells. Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3101-12. Epub 2007 Dec 7. PubMed PMID: 18065490.

53: Jackman KM, Frye CB, Hunger SP. Flavopiridol displays preclinical activity in acute lymphoblastic leukemia. Pediatr Blood Cancer. 2008 Apr;50(4):772-8. PubMed PMID: 18000861.

54: Billard C, Menasria F, Quiney C, Faussat AM, Kolb JP. Flavopiridol-induced iNOS downregulation during apoptosis of chronic lymphocytic leukemia cells is caspase-dependent. Leuk Res. 2008 May;32(5):755-60. Epub 2007 Nov 5. PubMed PMID: 17981326.

55: Fornier MN, Rathkopf D, Shah M, Patil S, O'Reilly E, Tse AN, Hudis C, Lefkowitz R, Kelsen DP, Schwartz GK. Phase I dose-finding study of weekly docetaxel followed by flavopiridol for patients with advanced solid tumors. Clin Cancer Res. 2007 Oct 1;13(19):5841-6. PubMed PMID: 17908977.

56: Christian BA, Grever MR, Byrd JC, Lin TS. Flavopiridol in the treatment of chronic lymphocytic leukemia. Curr Opin Oncol. 2007 Nov;19(6):573-8. Review. PubMed PMID: 17906454.

57: Karp JE, Smith BD, Levis MJ, Gore SD, Greer J, Hattenburg C, Briel J, Jones RJ, Wright JJ, Colevas AD. Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia. Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4467-73. PubMed PMID: 17671131.

58: Biglione S, Byers SA, Price JP, Nguyen VT, Bensaude O, Price DH, Maury W. Inhibition of HIV-1 replication by P-TEFb inhibitors DRB, seliciclib and flavopiridol correlates with release of free P-TEFb from the large, inactive form of the complex. Retrovirology. 2007 Jul 11;4:47. PubMed PMID: 17625008; PubMed Central PMCID: PMC1948018.

59: Li Y, Tanaka K, Li X, Okada T, Nakamura T, Takasaki M, Yamamoto S, Oda Y, Tsuneyoshi M, Iwamoto Y. Cyclin-dependent kinase inhibitor, flavopiridol, induces apoptosis and inhibits tumor growth in drug-resistant osteosarcoma and Ewing's family tumor cells. Int J Cancer. 2007 Sep 15;121(6):1212-8. PubMed PMID: 17520676.

60: Beesley AH, Palmer ML, Ford J, Weller RE, Cummings AJ, Freitas JR, Firth MJ, Perera KU, de Klerk NH, Kees UR. In vitro cytotoxicity of nelarabine, clofarabine and flavopiridol in paediatric acute lymphoblastic leukaemia. Br J Haematol. 2007 Apr;137(2):109-16. Erratum in: Br J Haematol. 2011 Aug;154(4):541. PubMed PMID: 17391490.

61: Rosato RR, Almenara JA, Kolla SS, Maggio SC, Coe S, Giménez MS, Dent P, Grant S. Mechanism and functional role of XIAP and Mcl-1 down-regulation in flavopiridol/vorinostat antileukemic interactions. Mol Cancer Ther. 2007 Feb;6(2):692-702. PubMed PMID: 17308065.

62: Morris DG, Bramwell VH, Turcotte R, Figueredo AT, Blackstein ME, Verma S, Matthews S, Eisenhauer EA. A Phase II Study of Flavopiridol in Patients With Previously Untreated Advanced Soft Tissue Sarcoma. Sarcoma. 2006;2006:64374. PubMed PMID: 17251659; PubMed Central PMCID: PMC1698142.

63: Fandy TE, Ross DD, Gore SD, Srivastava RK. Flavopiridol synergizes TRAIL cytotoxicity by downregulation of FLIPL. Cancer Chemother Pharmacol. 2007 Aug;60(3):313-9. Epub 2006 Dec 23. PubMed PMID: 17187253.

64: Ahn YM, Vogeti L, Liu CJ, Santhapuram HK, White JM, Vasandani V, Mitscher LA, Lushington GH, Hanson PR, Powell DR, Himes RH, Roby KF, Ye Q, Georg GI. Design, synthesis, and antiproliferative and CDK2-cyclin a inhibitory activity of novel flavopiridol analogues. Bioorg Med Chem. 2007 Jan 15;15(2):702-13. Epub 2006 Nov 1. PubMed PMID: 17123821; PubMed Central PMCID: PMC1876666.

65: Sato S, Kajiyama Y, Sugano M, Iwanuma Y, Sonoue H, Matsumoto T, Tsurumaru M. Alvocidib (Flavopiridol) suppresses tumor growth in SCID mice with human esophageal cancer xenografts without inducing apoptosis. Surg Oncol. 2006 Aug;15(2):107-13. Epub 2006 Nov 13. PubMed PMID: 17097874.

66: Guo J, Zhou AW, Fu YC, Verma UN, Tripathy D, Frenkel EP, Becerra CR. Efficacy of sequential treatment of HCT116 colon cancer monolayers and xenografts with docetaxel, flavopiridol, and 5-fluorouracil. Acta Pharmacol Sin. 2006 Oct;27(10):1375-81. PubMed PMID: 17007746.

67: Byrd JC, Lin TS, Dalton JT, Wu D, Phelps MA, Fischer B, Moran M, Blum KA, Rovin B, Brooker-McEldowney M, Broering S, Schaaf LJ, Johnson AJ, Lucas DM, Heerema NA, Lozanski G, Young DC, Suarez JR, Colevas AD, Grever MR. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia. Blood. 2007 Jan 15;109(2):399-404. Epub 2006 Sep 26. PubMed PMID: 17003373; PubMed Central PMCID: PMC1785084.

68: Palacios C, Yerbes R, López-Rivas A. Flavopiridol induces cellular FLICE-inhibitory protein degradation by the proteasome and promotes TRAIL-induced early signaling and apoptosis in breast tumor cells. Cancer Res. 2006 Sep 1;66(17):8858-69. PubMed PMID: 16951203.

69: Reiner T, de las Pozas A, Perez-Stable C. Sequential combinations of flavopiridol and docetaxel inhibit prostate tumors, induce apoptosis, and decrease angiogenesis in the Ggamma/T-15 transgenic mouse model of prostate cancer. Prostate. 2006 Oct 1;66(14):1487-97. PubMed PMID: 16921509.

70: McAleer MF, Duffy KT, Davidson WR, Kari G, Dicker AP, Rodeck U, Wickstrom E. Antisense inhibition of cyclin D1 expression is equivalent to flavopiridol for radiosensitization of zebrafish embryos. Int J Radiat Oncol Biol Phys. 2006 Oct 1;66(2):546-51. Epub 2006 Aug 14. PubMed PMID: 16904844.

71: Miyashita K, Shiraki K, Fuke H, Inoue T, Yamanaka Y, Yamaguchi Y, Yamamoto N, Ito K, Sugimoto K, Nakano T. The cyclin-dependent kinase inhibitor flavopiridol sensitizes human hepatocellular carcinoma cells to TRAIL-induced apoptosis. Int J Mol Med. 2006 Aug;18(2):249-56. PubMed PMID: 16820931.

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84: Newcomb EW, Ali MA, Schnee T, Lan L, Lukyanov Y, Fowkes M, Miller DC, Zagzag D. Flavopiridol downregulates hypoxia-mediated hypoxia-inducible factor-1alpha expression in human glioma cells by a proteasome-independent pathway: implications for in vivo therapy. Neuro Oncol. 2005 Jul;7(3):225-35. PubMed PMID: 16053697; PubMed Central PMCID: PMC1871916.

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88: Verdaguer E, Jordà EG, Alvira D, Jiménez A, Canudas AM, Folch J, Rimbau V, Pallàs M, Camins A. Inhibition of multiple pathways accounts for the antiapoptotic effects of flavopiridol on potassium withdrawal-induced apoptosis in neurons. J Mol Neurosci. 2005;26(1):71-84. PubMed PMID: 15968087.

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90: Byrd JC, Peterson BL, Gabrilove J, Odenike OM, Grever MR, Rai K, Larson RA; Cancer and Leukemia Group B. Treatment of relapsed chronic lymphocytic leukemia by 72-hour continuous infusion or 1-hour bolus infusion of flavopiridol: results from Cancer and Leukemia Group B study 19805. Clin Cancer Res. 2005 Jun 1;11(11):4176-81. PubMed PMID: 15930354.

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92: Kim S, Wu HG, Shin JH, Park HJ, Kim IA, Kim IH. Enhancement of radiation effects by flavopiridol in uterine cervix cancer cells. Cancer Res Treat. 2005 Jun;37(3):191-5. Epub 2005 Jun 30. PubMed PMID: 19956502; PubMed Central PMCID: PMC2785412.

93: Flinn IW, Byrd JC, Bartlett N, Kipps T, Gribben J, Thomas D, Larson RA, Rai K, Petric R, Ramon-Suerez J, Gabrilove J, Grever MR. Flavopiridol administered as a 24-hour continuous infusion in chronic lymphocytic leukemia lacks clinical activity. Leuk Res. 2005 Nov;29(11):1253-7. PubMed PMID: 15916806.

94: Shah MA, Kortmansky J, Motwani M, Drobnjak M, Gonen M, Yi S, Weyerbacher A, Cordon-Cardo C, Lefkowitz R, Brenner B, O'Reilly E, Saltz L, Tong W, Kelsen DP, Schwartz GK. A phase I clinical trial of the sequential combination of irinotecan followed by flavopiridol. Clin Cancer Res. 2005 May 15;11(10):3836-45. PubMed PMID: 15897584.

95: Mayer F, Mueller S, Malenke E, Kuczyk M, Hartmann JT, Bokemeyer C. Induction of apoptosis by flavopiridol unrelated to cell cycle arrest in germ cell tumour derived cell lines. Invest New Drugs. 2005 Jun;23(3):205-11. PubMed PMID: 15868376.

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97: Cory AH, Somerville L, Cory JG. Blockage of cyclin cdk's, PKC and phosphoinositol 3-kinase pathways leads to augmentation of apoptosis in drug-resistant leukemia cells: evidence for interactive effects of flavopiridol, LY 294002, roscovitine,wortmannin and UCN-01. Anticancer Res. 2005 Jan-Feb;25(1A):101-6. Erratum in: Anticancer Res. 2005 May-Jun;25(3c):2599. PubMed PMID: 15816525.

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100: Najmi S, Korah R, Chandra R, Abdellatif M, Wieder R. Flavopiridol blocks integrin-mediated survival in dormant breast cancer cells. Clin Cancer Res. 2005 Mar 1;11(5):2038-46. PubMed PMID: 15756030.

101: Lechpammer M, Xu X, Ellis FH, Bhattacharaya N, Shapiro GI, Loda M. Flavopiridol reduces malignant transformation of the esophageal mucosa in p27 knockout mice. Oncogene. 2005 Mar 3;24(10):1683-8. PubMed PMID: 15674336.

102: Pei XY, Dai Y, Grant S. The small-molecule Bcl-2 inhibitor HA14-1 interacts synergistically with flavopiridol to induce mitochondrial injury and apoptosis in human myeloma cells through a free radical-dependent and Jun NH2-terminal kinase-dependent mechanism. Mol Cancer Ther. 2004 Dec;3(12):1513-24. PubMed PMID: 15634644.

103: Puppo M, Pastorino S, Melillo G, Pezzolo A, Varesio L, Bosco MC. Induction of apoptosis by flavopiridol in human neuroblastoma cells is enhanced under hypoxia and associated with N-myc proto-oncogene down-regulation. Clin Cancer Res. 2004 Dec 15;10(24):8704-19. PubMed PMID: 15623656.

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105: Blagosklonny MV. Flavopiridol, an inhibitor of transcription: implications, problems and solutions. Cell Cycle. 2004 Dec;3(12):1537-42. Epub 2004 Dec 1. Review. PubMed PMID: 15539947.

106: Pallàs M, Verdaguer E, Jordà EG, Jiménez A, Canudas AM, Camins A. Flavopiridol: an antitumor drug with potential application in the treatment of neurodegenerative diseases. Med Hypotheses. 2005;64(1):120-3. PubMed PMID: 15533627.

107: Rosato RR, Dai Y, Almenara JA, Maggio SC, Grant S. Potent antileukemic interactions between flavopiridol and TRAIL/Apo2L involve flavopiridol-mediated XIAP downregulation. Leukemia. 2004 Nov;18(11):1780-8. PubMed PMID: 15385934.

108: Zhang M, Zhang Z, Goldman CK, Janik J, Waldmann TA. Combination therapy for adult T-cell leukemia-xenografted mice: flavopiridol and anti-CD25 monoclonal antibody. Blood. 2005 Feb 1;105(3):1231-6. Epub 2004 Sep 21. PubMed PMID: 15383455.

109: Tan AR, Yang X, Berman A, Zhai S, Sparreboom A, Parr AL, Chow C, Brahim JS, Steinberg SM, Figg WD, Swain SM. Phase I trial of the cyclin-dependent kinase inhibitor flavopiridol in combination with docetaxel in patients with metastatic breast cancer. Clin Cancer Res. 2004 Aug 1;10(15):5038-47. PubMed PMID: 15297405.

110: Grant S, Dent P. Gene profiling and the cyclin-dependent kinase inhibitor flavopiridol: what's in a name? Mol Cancer Ther. 2004 Jul;3(7):873-5. Review. PubMed PMID: 15252148.

111: Lü X, Burgan WE, Cerra MA, Chuang EY, Tsai MH, Tofilon PJ, Camphausen K. Transcriptional signature of flavopiridol-induced tumor cell death. Mol Cancer Ther. 2004 Jul;3(7):861-72. PubMed PMID: 15252147.

112: Gao N, Dai Y, Rahmani M, Dent P, Grant S. Contribution of disruption of the nuclear factor-kappaB pathway to induction of apoptosis in human leukemia cells by histone deacetylase inhibitors and flavopiridol. Mol Pharmacol. 2004 Oct;66(4):956-63. Epub 2004 Jul 2. PubMed PMID: 15235103.

113: Mason KA, Hunter NR, Raju U, Ariga H, Husain A, Valdecanas D, Neal R, Ang KK, Milas L. Flavopiridol increases therapeutic ratio of radiotherapy by preferentially enhancing tumor radioresponse. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):1181-9. PubMed PMID: 15234054.

114: Shapiro GI. Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol. Clin Cancer Res. 2004 Jun 15;10(12 Pt 2):4270s-4275s. Review. PubMed PMID: 15217973.

115: Jaschke B, Milz S, Vogeser M, Michaelis C, Vorpahl M, Schömig A, Kastrati A, Wessely R. Local cyclin-dependent kinase inhibition by flavopiridol inhibits coronary artery smooth muscle cell proliferation and migration: Implications for the applicability on drug-eluting stents to prevent neointima formation following vascular injury. FASEB J. 2004 Aug;18(11):1285-7. Epub 2004 Jun 4. PubMed PMID: 15180955.

116: Newcomb EW. Flavopiridol: pleiotropic biological effects enhance its anti-cancer activity. Anticancer Drugs. 2004 Jun;15(5):411-9. Review. PubMed PMID: 15166614.

117: Demidenko ZN, Blagosklonny MV. Flavopiridol induces p53 via initial inhibition of Mdm2 and p21 and, independently of p53, sensitizes apoptosis-reluctant cells to tumor necrosis factor. Cancer Res. 2004 May 15;64(10):3653-60. PubMed PMID: 15150125.

118: Burdette-Radoux S, Tozer RG, Lohmann RC, Quirt I, Ernst DS, Walsh W, Wainman N, Colevas AD, Eisenhauer EA. Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma. Invest New Drugs. 2004 Aug;22(3):315-22. PubMed PMID: 15122079.

119: Kim JC, Saha D, Cao Q, Choy H. Enhancement of radiation effects by combined docetaxel and flavopiridol treatment in lung cancer cells. Radiother Oncol. 2004 May;71(2):213-21. PubMed PMID: 15110456.

120: Camphausen K, Brady KJ, Burgan WE, Cerra MA, Russell JS, Bull EE, Tofilon PJ. Flavopiridol enhances human tumor cell radiosensitivity and prolongs expression of gammaH2AX foci. Mol Cancer Ther. 2004 Apr;3(4):409-16. PubMed PMID: 15078984.

121: Honoki K, Yoshitani K, Tsujiuchi T, Mori T, Tsutsumi M, Morishita T, Takakura Y, Mii Y. Growth inhibition and induction of apoptosis by flavopiridol in rat lung adenocarcinoma, osteosarcoma and malignant fibrous histiocytoma cell lines. Oncol Rep. 2004 May;11(5):1025-30. PubMed PMID: 15069542.

122: Dai Y, Rahmani M, Pei XY, Dent P, Grant S. Bortezomib and flavopiridol interact synergistically to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate through both Bcr/Abl-dependent and -independent mechanisms. Blood. 2004 Jul 15;104(2):509-18. Epub 2004 Mar 23. PubMed PMID: 15039284.

123: Billard C, Quiney C, Tang R, Kern C, Ajchenbaum-Cymbalista F, Dauzonne D, Kolb JP. The inducible NO synthase is downregulated during apoptosis of malignant cells from B-cell chronic lymphocytic leukemia induced by flavopiridol and polyphenols. Ann N Y Acad Sci. 2003 Dec;1010:381-3. PubMed PMID: 15033756.

124: Nguyen DM, Schrump WD, Chen GA, Tsai W, Nguyen P, Trepel JB, Schrump DS. Abrogation of p21 expression by flavopiridol enhances depsipeptide-mediated apoptosis in malignant pleural mesothelioma cells. Clin Cancer Res. 2004 Mar 1;10(5):1813-25. PubMed PMID: 15014036.

125: Rosato RR, Almenara JA, Yu C, Grant S. Evidence of a functional role for p21WAF1/CIP1 down-regulation in synergistic antileukemic interactions between the histone deacetylase inhibitor sodium butyrate and flavopiridol. Mol Pharmacol. 2004 Mar;65(3):571-81. PubMed PMID: 14978235.

126: Liu G, Gandara DR, Lara PN Jr, Raghavan D, Doroshow JH, Twardowski P, Kantoff P, Oh W, Kim K, Wilding G. A Phase II trial of flavopiridol (NSC #649890) in patients with previously untreated metastatic androgen-independent prostate cancer. Clin Cancer Res. 2004 Feb 1;10(3):924-8. PubMed PMID: 14871968.

127: Witters LM, Myers A, Lipton A. Combining flavopiridol with various signal transduction inhibitors. Oncol Rep. 2004 Mar;11(3):693-8. PubMed PMID: 14767524.

128: Newcomb EW, Tamasdan C, Entzminger Y, Arena E, Schnee T, Kim M, Crisan D, Lukyanov Y, Miller DC, Zagzag D. Flavopiridol inhibits the growth of GL261 gliomas in vivo: implications for malignant glioma therapy. Cell Cycle. 2004 Feb;3(2):230-4. PubMed PMID: 14712094.

129: Jäger W, Gehring E, Hagenauer B, Aust S, Senderowicz A, Thalhammer T. The role of hepatic Mrp2 in the interaction of flavopiridol and bilirubin: impact on therapy. Int J Clin Pharmacol Ther. 2003 Dec;41(12):610-1. PubMed PMID: 14692715.

130: Jung C, Motwani M, Kortmansky J, Sirotnak FM, She Y, Gonen M, Haimovitz-Friedman A, Schwartz GK. The cyclin-dependent kinase inhibitor flavopiridol potentiates gamma-irradiation-induced apoptosis in colon and gastric cancer cells. Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):6052-61. PubMed PMID: 14676132.

131: Lin TS, Porcu P. Flavopiridol: where do we stand in chronic lymphocytic leukemia? Leukemia. 2004 Feb;18(2):243-6. PubMed PMID: 14671637.

132: Takada Y, Aggarwal BB. Flavopiridol inhibits NF-kappaB activation induced by various carcinogens and inflammatory agents through inhibition of IkappaBalpha kinase and p65 phosphorylation: abrogation of cyclin D1, cyclooxygenase-2, and matrix metalloprotease-9. J Biol Chem. 2004 Feb 6;279(6):4750-9. Epub 2003 Nov 20. PubMed PMID: 14630924.

133: Jiang J, Matranga CB, Cai D, Latham VM Jr, Zhang X, Lowell AM, Martelli F, Shapiro GI. Flavopiridol-induced apoptosis during S phase requires E2F-1 and inhibition of cyclin A-dependent kinase activity. Cancer Res. 2003 Nov 1;63(21):7410-22. PubMed PMID: 14612540.

134: Verdaguer E, Jiménez A, Canudas AM, Jordà EG, Sureda FX, Pallàs M, Camins A. Inhibition of cell cycle pathway by flavopiridol promotes survival of cerebellar granule cells after an excitotoxic treatment. J Pharmacol Exp Ther. 2004 Feb;308(2):609-16. Epub 2003 Nov 10. PubMed PMID: 14610234.

135: Incles CM, Schultes CM, Kelland LR, Neidle S. Acquired cellular resistance to flavopiridol in a human colon carcinoma cell line involves up-regulation of the telomerase catalytic subunit and telomere elongation. Sensitivity of resistant cells to combination treatment with a telomerase inhibitor. Mol Pharmacol. 2003 Nov;64(5):1101-8. PubMed PMID: 14573759.

136: Dai Y, Rahmani M, Grant S. Proteasome inhibitors potentiate leukemic cell apoptosis induced by the cyclin-dependent kinase inhibitor flavopiridol through a SAPK/JNK- and NF-kappaB-dependent process. Oncogene. 2003 Oct 16;22(46):7108-22. PubMed PMID: 14562039.

137: Litz J, Carlson P, Warshamana-Greene GS, Grant S, Krystal GW. Flavopiridol potently induces small cell lung cancer apoptosis during S phase in a manner that involves early mitochondrial dysfunction. Clin Cancer Res. 2003 Oct 1;9(12):4586-94. PubMed PMID: 14555534.

138: Billard C, Kern C, Tang R, Ajchenbaum-Cymbalista F, Kolb JP. Flavopiridol downregulates the expression of both the inducible NO synthase and p27(kip1) in malignant cells from B-cell chronic lymphocytic leukemia. Leukemia. 2003 Dec;17(12):2435-43. PubMed PMID: 14523476.

139: Rudek MA, Bauer KS Jr, Lush RM 3rd, Stinson SF, Senderowicz AM, Headlee DJ, Arbuck SG, Cox MC, Murgo AJ, Sausville EA, Figg WD. Clinical pharmacology of flavopiridol following a 72-hour continuous infusion. Ann Pharmacother. 2003 Oct;37(10):1369-74. PubMed PMID: 14519054.

140: Jäger W, Gehring E, Hagenauer B, Aust S, Senderowicz A, Thalhammer T. Biliary excretion of flavopiridol and its glucuronides in the isolated perfused rat liver: role of multidrug resistance protein 2 (Mrp2). Life Sci. 2003 Oct 17;73(22):2841-54. PubMed PMID: 14511769.

141: Nakanishi T, Karp JE, Tan M, Doyle LA, Peters T, Yang W, Wei D, Ross DD. Quantitative analysis of breast cancer resistance protein and cellular resistance to flavopiridol in acute leukemia patients. Clin Cancer Res. 2003 Aug 15;9(9):3320-8. PubMed PMID: 12960118.

142: Villeneuve L, Girard H, Fortier LC, Gagné JF, Guillemette C. Novel functional polymorphisms in the UGT1A7 and UGT1A9 glucuronidating enzymes in Caucasian and African-American subjects and their impact on the metabolism of 7-ethyl-10-hydroxycamptothecin and flavopiridol anticancer drugs. J Pharmacol Exp Ther. 2003 Oct;307(1):117-28. Epub 2003 Aug 27. PubMed PMID: 12944498.

143: Jorda EG, Verdaguer E, Canudas AM, Jiménez A, Bruna A, Caelles C, Bravo R, Escubedo E, Pubill D, Camarasa J, Pallàs M, Camins A. Neuroprotective action of flavopiridol, a cyclin-dependent kinase inhibitor, in colchicine-induced apoptosis. Neuropharmacology. 2003 Oct;45(5):672-83. PubMed PMID: 12941380.

144: Aklilu M, Kindler HL, Donehower RC, Mani S, Vokes EE. Phase II study of flavopiridol in patients with advanced colorectal cancer. Ann Oncol. 2003 Aug;14(8):1270-3. PubMed PMID: 12881391.

145: Nahta R, Trent S, Yang C, Schmidt EV. Epidermal growth factor receptor expression is a candidate target of the synergistic combination of trastuzumab and flavopiridol in breast cancer. Cancer Res. 2003 Jul 1;63(13):3626-31. PubMed PMID: 12839951.

146: Motwani M, Rizzo C, Sirotnak F, She Y, Schwartz GK. Flavopiridol enhances the effect of docetaxel in vitro and in vivo in human gastric cancer cells. Mol Cancer Ther. 2003 Jun;2(6):549-55. PubMed PMID: 12813134.

147: Raju U, Nakata E, Mason KA, Ang KK, Milas L. Flavopiridol, a cyclin-dependent kinase inhibitor, enhances radiosensitivity of ovarian carcinoma cells. Cancer Res. 2003 Jun 15;63(12):3263-7. PubMed PMID: 12810657.

148: Robinson WA, Miller TL, Harrold EA, Bemis LT, Brady BM, Nelson RP. The effect of flavopiridol on the growth of p16+ and p16- melanoma cell lines. Melanoma Res. 2003 Jun;13(3):231-8. PubMed PMID: 12777976.

149: Nguyen DM, Schrump WD, Tsai WS, Chen A, Stewart JH 4th, Steiner F, Schrump DS. Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: activation of the mitochondria-dependent death-signaling pathway. J Thorac Cardiovasc Surg. 2003 May;125(5):1132-42. PubMed PMID: 12771887.

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151: Newcomb EW, Tamasdan C, Entzminger Y, Alonso J, Friedlander D, Crisan D, Miller DC, Zagzag D. Flavopiridol induces mitochondrial-mediated apoptosis in murine glioma GL261 cells via release of cytochrome c and apoptosis inducing factor. Cell Cycle. 2003 May-Jun;2(3):243-50. PubMed PMID: 12734434.

152: Pepper C, Thomas A, Hoy T, Tighe J, Culligan D, Fegan C, Bentley P. Leukemic and non-leukemic lymphocytes from patients with Li Fraumeni syndrome demonstrate loss of p53 function, Bcl-2 family dysregulation and intrinsic resistance to conventional chemotherapeutic drugs but not flavopiridol. Cell Cycle. 2003 Jan-Feb;2(1):53-8. PubMed PMID: 12695689.

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154: Nelson PJ, D'Agati VD, Gries JM, Suarez JR, Gelman IH. Amelioration of nephropathy in mice expressing HIV-1 genes by the cyclin-dependent kinase inhibitor flavopiridol. J Antimicrob Chemother. 2003 Apr;51(4):921-9. Epub 2003 Mar 13. PubMed PMID: 12654740.

155: Alonso M, Tamasdan C, Miller DC, Newcomb EW. Flavopiridol induces apoptosis in glioma cell lines independent of retinoblastoma and p53 tumor suppressor pathway alterations by a caspase-independent pathway. Mol Cancer Ther. 2003 Feb;2(2):139-50. PubMed PMID: 12589031.

156: Messmann RA, Ullmann CD, Lahusen T, Kalehua A, Wasfy J, Melillo G, Ding I, Headlee D, Figg WD, Sausville EA, Senderowicz AM. Flavopiridol-related proinflammatory syndrome is associated with induction of interleukin-6. Clin Cancer Res. 2003 Feb;9(2):562-70. PubMed PMID: 12576419.

157: Zhai S, Sausville EA, Senderowicz AM, Ando Y, Headlee D, Messmann RA, Arbuck S, Murgo AJ, Melillo G, Fuse E, Figg WD. Clinical pharmacology and pharmacogenetics of flavopiridol 1-h i.v. infusion in patients with refractory neoplasms. Anticancer Drugs. 2003 Feb;14(2):125-35. PubMed PMID: 12569299.

158: Kim DM, Koo SY, Jeon K, Kim MH, Lee J, Hong CY, Jeong S. Rapid induction of apoptosis by combination of flavopiridol and tumor necrosis factor (TNF)-alpha or TNF-related apoptosis-inducing ligand in human cancer cell lines. Cancer Res. 2003 Feb 1;63(3):621-6. PubMed PMID: 12566305.

159: Karp JE, Ross DD, Yang W, Tidwell ML, Wei Y, Greer J, Mann DL, Nakanishi T, Wright JJ, Colevas AD. Timed sequential therapy of acute leukemia with flavopiridol: in vitro model for a phase I clinical trial. Clin Cancer Res. 2003 Jan;9(1):307-15. PubMed PMID: 12538483.

160: Cartee L, Maggio SC, Smith R, Sankala HM, Dent P, Grant S. Protein kinase C-dependent activation of the tumor necrosis factor receptor-mediated extrinsic cell death pathway underlies enhanced apoptosis in human myeloid leukemia cells exposed to bryostatin 1 and flavopiridol. Mol Cancer Ther. 2003 Jan;2(1):83-93. PubMed PMID: 12533676.

161: Ma Y, Cress WD, Haura EB. Flavopiridol-induced apoptosis is mediated through up-regulation of E2F1 and repression of Mcl-1. Mol Cancer Ther. 2003 Jan;2(1):73-81. PubMed PMID: 12533675.

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163: Wittmann S, Bali P, Donapaty S, Nimmanapalli R, Guo F, Yamaguchi H, Huang M, Jove R, Wang HG, Bhalla K. Flavopiridol down-regulates antiapoptotic proteins and sensitizes human breast cancer cells to epothilone B-induced apoptosis. Cancer Res. 2003 Jan 1;63(1):93-9. PubMed PMID: 12517783.

164: Wu K, Wang C, D'Amico M, Lee RJ, Albanese C, Pestell RG, Mani S. Flavopiridol and trastuzumab synergistically inhibit proliferation of breast cancer cells: association with selective cooperative inhibition of cyclin D1-dependent kinase and Akt signaling pathways. Mol Cancer Ther. 2002 Jul;1(9):695-706. PubMed PMID: 12479366.

165: Rosato RR, Almenara JA, Cartee L, Betts V, Chellappan SP, Grant S. The cyclin-dependent kinase inhibitor flavopiridol disrupts sodium butyrate-induced p21WAF1/CIP1 expression and maturation while reciprocally potentiating apoptosis in human leukemia cells. Mol Cancer Ther. 2002 Feb;1(4):253-66. PubMed PMID: 12467221.

166: Mihara M, Shintani S, Nakashiro K, Hamakawa H. Flavopiridol, a cyclin dependent kinase (CDK) inhibitor, induces apoptosis by regulating Bcl-x in oral cancer cells. Oral Oncol. 2003 Jan;39(1):49-55. PubMed PMID: 12457721.

167: Thomas JP, Tutsch KD, Cleary JF, Bailey HH, Arzoomanian R, Alberti D, Simon K, Feierabend C, Binger K, Marnocha R, Dresen A, Wilding G. Phase I clinical and pharmacokinetic trial of the cyclin-dependent kinase inhibitor flavopiridol. Cancer Chemother Pharmacol. 2002 Dec;50(6):465-72. Epub 2002 Oct 2. PubMed PMID: 12451473.

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169: Gojo I, Zhang B, Fenton RG. The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in multiple myeloma cells through transcriptional repression and down-regulation of Mcl-1. Clin Cancer Res. 2002 Nov;8(11):3527-38. PubMed PMID: 12429644.

170: Colevas D, Blaylock B, Gravell A. Clinical trials referral resource. Flavopiridol. Oncology (Williston Park). 2002 Sep;16(9):1204-5, 1210-2, 1214. PubMed PMID: 12380947.

171: Tan AR, Headlee D, Messmann R, Sausville EA, Arbuck SG, Murgo AJ, Melillo G, Zhai S, Figg WD, Swain SM, Senderowicz AM. Phase I clinical and pharmacokinetic study of flavopiridol administered as a daily 1-hour infusion in patients with advanced neoplasms. J Clin Oncol. 2002 Oct 1;20(19):4074-82. PubMed PMID: 12351605.

172: Yu C, Krystal G, Dent P, Grant S. Flavopiridol potentiates STI571-induced mitochondrial damage and apoptosis in BCR-ABL-positive human leukemia cells. Clin Cancer Res. 2002 Sep;8(9):2976-84. PubMed PMID: 12231544.

173: Zhai S, Sausville E, Figg WD. A high-performance liquid chromatography method using ultraviolet detection for the quantitation of flavopiridol from human plasma. Biomed Chromatogr. 2002 Sep;16(6):379-82. PubMed PMID: 12228893.

174: Decker RH, Wang S, Dai Y, Dent P, Grant S. Loss of the Bcl-2 phosphorylation loop domain is required to protect human myeloid leukemia cells from flavopiridol-mediated mitochondrial damage and apoptosis. Cancer Biol Ther. 2002 Mar-Apr;1(2):136-44. PubMed PMID: 12170773.

175: Senderowicz AM. The cell cycle as a target for cancer therapy: basic and clinical findings with the small molecule inhibitors flavopiridol and UCN-01. Oncologist. 2002;7 Suppl 3:12-9. Review. PubMed PMID: 12165651.

176: Lin TS, Howard OM, Neuberg DS, Kim HH, Shipp MA. Seventy-two hour continuous infusion flavopiridol in relapsed and refractory mantle cell lymphoma. Leuk Lymphoma. 2002 Apr;43(4):793-7. PubMed PMID: 12153166.

177: Tan AR, Swain SM. Review of flavopiridol, a cyclin-dependent kinase inhibitor, as breast cancer therapy. Semin Oncol. 2002 Jun;29(3 Suppl 11):77-85. Review. PubMed PMID: 12138401.

178: Rapella A, Negrioli A, Melillo G, Pastorino S, Varesio L, Bosco MC. Flavopiridol inhibits vascular endothelial growth factor production induced by hypoxia or picolinic acid in human neuroblastoma. Int J Cancer. 2002 Jun 10;99(5):658-64. PubMed PMID: 12115498.

179: Almenara J, Rosato R, Grant S. Synergistic induction of mitochondrial damage and apoptosis in human leukemia cells by flavopiridol and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). Leukemia. 2002 Jul;16(7):1331-43. PubMed PMID: 12094258.

180: Ramírez J, Iyer L, Journault K, Bélanger P, Innocenti F, Ratain MJ, Guillemette C. In vitro characterization of hepatic flavopiridol metabolism using human liver microsomes and recombinant UGT enzymes. Pharm Res. 2002 May;19(5):588-94. PubMed PMID: 12069159.

181: de Azevedo WF Jr, Canduri F, da Silveira NJ. Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol. Biochem Biophys Res Commun. 2002 Apr 26;293(1):566-71. PubMed PMID: 12054639.

182: Cartee L, Smith R, Dai Y, Rahmani M, Rosato R, Almenara J, Dent P, Grant S. Synergistic induction of apoptosis in human myeloid leukemia cells by phorbol 12-myristate 13-acetate and flavopiridol proceeds via activation of both the intrinsic and tumor necrosis factor-mediated extrinsic cell death pathways. Mol Pharmacol. 2002 Jun;61(6):1313-21. PubMed PMID: 12021392.

183: Zhai S, Senderowicz AM, Sausville EA, Figg WD. Flavopiridol, a novel cyclin-dependent kinase inhibitor, in clinical development. Ann Pharmacother. 2002 May;36(5):905-11. Review. PubMed PMID: 11978170.

184: Schoepfer J, Fretz H, Chaudhuri B, Muller L, Seeber E, Meijer L, Lozach O, Vangrevelinghe E, Furet P. Structure-based design and synthesis of 2-benzylidene-benzofuran-3-ones as flavopiridol mimics. J Med Chem. 2002 Apr 25;45(9):1741-7. PubMed PMID: 11960485.

185: Schwartz GK, O'Reilly E, Ilson D, Saltz L, Sharma S, Tong W, Maslak P, Stoltz M, Eden L, Perkins P, Endres S, Barazzoul J, Spriggs D, Kelsen D. Phase I study of the cyclin-dependent kinase inhibitor flavopiridol in combination with paclitaxel in patients with advanced solid tumors. J Clin Oncol. 2002 Apr 15;20(8):2157-70. PubMed PMID: 11956278.

186: Nahta R, Iglehart JD, Kempkes B, Schmidt EV. Rate-limiting effects of Cyclin D1 in transformation by ErbB2 predicts synergy between herceptin and flavopiridol. Cancer Res. 2002 Apr 15;62(8):2267-71. PubMed PMID: 11956082.

187: Matranga CB, Shapiro GI. Selective sensitization of transformed cells to flavopiridol-induced apoptosis following recruitment to S-phase. Cancer Res. 2002 Mar 15;62(6):1707-17. PubMed PMID: 11912144.

188: Wang HK. Flavopiridol. National Cancer Institute. Curr Opin Investig Drugs. 2001 Aug;2(8):1149-55. Review. PubMed PMID: 11892928.

189: Semenov I, Akyuz C, Roginskaya V, Chauhan D, Corey SJ. Growth inhibition and apoptosis of myeloma cells by the CDK inhibitor flavopiridol. Leuk Res. 2002 Mar;26(3):271-80. PubMed PMID: 11792416.

190: Motwani M, Jung C, Sirotnak FM, She Y, Shah MA, Gonen M, Schwartz GK. Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in Hct116 colon cancer monolayers and xenografts. Clin Cancer Res. 2001 Dec;7(12):4209-19. PubMed PMID: 11751522.

191: Smith V, Raynaud F, Workman P, Kelland LR. Characterization of a human colorectal carcinoma cell line with acquired resistance to flavopiridol. Mol Pharmacol. 2001 Nov;60(5):885-93. PubMed PMID: 11641415.

192: Lam LT, Pickeral OK, Peng AC, Rosenwald A, Hurt EM, Giltnane JM, Averett LM, Zhao H, Davis RE, Sathyamoorthy M, Wahl LM, Harris ED, Mikovits JA, Monks AP, Hollingshead MG, Sausville EA, Staudt LM. Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol. Genome Biol. 2001;2(10):RESEARCH0041. Epub 2001 Sep 13. PubMed PMID: 11597333; PubMed Central PMCID: PMC57796.

193: Jung CP, Motwani MV, Schwartz GK. Flavopiridol increases sensitization to gemcitabine in human gastrointestinal cancer cell lines and correlates with down-regulation of ribonucleotide reductase M2 subunit. Clin Cancer Res. 2001 Aug;7(8):2527-36. PubMed PMID: 11489836.

194: Rapoport AP, Simons-Evelyn M, Chen T, Sidell R, Luhowskyj S, Rosell K, Obrig T, Hicks D, Hinkle PM, Nahm M, Insel RA, Abboud CN. Flavopiridol induces apoptosis and caspase-3 activation of a newly characterized Burkitt's lymphoma cell line containing mutant p53 genes. Blood Cells Mol Dis. 2001 May-Jun;27(3):610-24. PubMed PMID: 11482875.

195: Pepper C, Thomas A, Hoy T, Fegan C, Bentley P. Flavopiridol circumvents Bcl-2 family mediated inhibition of apoptosis and drug resistance in B-cell chronic lymphocytic leukaemia. Br J Haematol. 2001 Jul;114(1):70-7. PubMed PMID: 11472347.

196: Decker RH, Dai Y, Grant S. The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in human leukemia cells (U937) through the mitochondrial rather than the receptor-mediated pathway. Cell Death Differ. 2001 Jul;8(7):715-24. PubMed PMID: 11464216.

197: Chao SH, Price DH. Flavopiridol inactivates P-TEFb and blocks most RNA polymerase II transcription in vivo. J Biol Chem. 2001 Aug 24;276(34):31793-9. Epub 2001 Jun 28. PubMed PMID: 11431468.

198: Shapiro GI, Supko JG, Patterson A, Lynch C, Lucca J, Zacarola PF, Muzikansky A, Wright JJ, Lynch TJ Jr, Rollins BJ. A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer. Clin Cancer Res. 2001 Jun;7(6):1590-9. PubMed PMID: 11410495.

199: Kaiser A, Nishi K, Gorin FA, Walsh DA, Bradbury EM, Schnier JB. The cyclin-dependent kinase (CDK) inhibitor flavopiridol inhibits glycogen phosphorylase. Arch Biochem Biophys. 2001 Feb 15;386(2):179-87. PubMed PMID: 11368340.

200: Boerner SA, Tourne ME, Kaufmann SH, Bible KC. Effect of P-glycoprotein on flavopiridol sensitivity. Br J Cancer. 2001 May 18;84(10):1391-6. PubMed PMID: 11355953; PubMed Central PMCID: PMC2363628.

201: Sedlacek HH. Mechanisms of action of flavopiridol. Crit Rev Oncol Hematol. 2001 May;38(2):139-70. Review. PubMed PMID: 11311660.

202: Cartee L, Wang Z, Decker RH, Chellappan SP, Fusaro G, Hirsch KG, Sankala HM, Dent P, Grant S. The cyclin-dependent kinase inhibitor (CDKI) flavopiridol disrupts phorbol 12-myristate 13-acetate-induced differentiation and CDKI expression while enhancing apoptosis in human myeloid leukemia cells. Cancer Res. 2001 Mar 15;61(6):2583-91. PubMed PMID: 11289135.

203: Li W, Fan J, Bertino JR. Selective sensitization of retinoblastoma protein-deficient sarcoma cells to doxorubicin by flavopiridol-mediated inhibition of cyclin-dependent kinase 2 kinase activity. Cancer Res. 2001 Mar 15;61(6):2579-82. PubMed PMID: 11289134.

204: Schwartz GK, Ilson D, Saltz L, O'Reilly E, Tong W, Maslak P, Werner J, Perkins P, Stoltz M, Kelsen D. Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma. J Clin Oncol. 2001 Apr 1;19(7):1985-92. PubMed PMID: 11283131.

205: Hagenauer B, Salamon A, Thalhammer T, Kunert O, Haslinger E, Klingler P, Senderowicz AM, Sausville EA, Jäger W. In vitro glucuronidation of the cyclin-dependent kinase inhibitor flavopiridol by rat and human liver microsomes: involvement of UDP-glucuronosyltransferases 1A1 and 1A9. Drug Metab Dispos. 2001 Apr;29(4 Pt 1):407-14. PubMed PMID: 11259324.

206: Kahn ME, Senderowicz A, Sausville EA, Barrett KE. Possible mechanisms of diarrheal side effects associated with the use of a novel chemotherapeutic agent, flavopiridol. Clin Cancer Res. 2001 Feb;7(2):343-9. PubMed PMID: 11234889.

207: Robey RW, Medina-Pérez WY, Nishiyama K, Lahusen T, Miyake K, Litman T, Senderowicz AM, Ross DD, Bates SE. Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. Clin Cancer Res. 2001 Jan;7(1):145-52. PubMed PMID: 11205902.

208: Li P, Patel H, Tabibi SE, Vishnuvajjala R, Yalkowsky SH. Evaluation of intravenous flavopiridol formulations. PDA J Pharm Sci Technol. 1999 May-Jun;53(3):137-40. PubMed PMID: 10754703.

209: Kelland LR. Flavopiridol, the first cyclin-dependent kinase inhibitor to enter the clinic: current status. Expert Opin Investig Drugs. 2000 Dec;9(12):2903-11. Review. PubMed PMID: 11093360.

210: Lansiaux A, Bailly C. [Flavopiridol, a cyclin-dependent kinase inhibitor]. Bull Cancer. 2000 Oct;87(10):697-701. Review. French. PubMed PMID: 11084532.

211: Innocenti F, Stadler WM, Iyer L, Ramírez J, Vokes EE, Ratain MJ. Flavopiridol metabolism in cancer patients is associated with the occurrence of diarrhea. Clin Cancer Res. 2000 Sep;6(9):3400-5. PubMed PMID: 10999721.

212: Li Y, Chinni SR, Senderowicz AM, Sarkar FH. Induction of growth inhibition and apoptosis in prostate cancer cells by flavopiridol. Int J Oncol. 2000 Oct;17(4):755-9. PubMed PMID: 10995888.

213: Oikonomakos NG, Schnier JB, Zographos SE, Skamnaki VT, Tsitsanou KE, Johnson LN. Flavopiridol inhibits glycogen phosphorylase by binding at the inhibitor site. J Biol Chem. 2000 Nov 3;275(44):34566-73. PubMed PMID: 10924512.

214: Chao SH, Fujinaga K, Marion JE, Taube R, Sausville EA, Senderowicz AM, Peterlin BM, Price DH. Flavopiridol inhibits P-TEFb and blocks HIV-1 replication. J Biol Chem. 2000 Sep 15;275(37):28345-8. PubMed PMID: 10906320.

215: Achenbach TV, Müller R, Slater EP. Bcl-2 independence of flavopiridol-induced apoptosis. Mitochondrial depolarization in the absence of cytochrome c release. J Biol Chem. 2000 Oct 13;275(41):32089-97. PubMed PMID: 10896673.

216: Kitada S, Zapata JM, Andreeff M, Reed JC. Protein kinase inhibitors flavopiridol and 7-hydroxy-staurosporine down-regulate antiapoptosis proteins in B-cell chronic lymphocytic leukemia. Blood. 2000 Jul 15;96(2):393-7. PubMed PMID: 10887097.

217: Murthi KK, Dubay M, McClure C, Brizuela L, Boisclair MD, Worland PJ, Mansuri MM, Pal K. Structure-activity relationship studies of flavopiridol analogues. Bioorg Med Chem Lett. 2000 May 15;10(10):1037-41. PubMed PMID: 10843211.

218: Bible KC, Bible RH Jr, Kottke TJ, Svingen PA, Xu K, Pang YP, Hajdu E, Kaufmann SH. Flavopiridol binds to duplex DNA. Cancer Res. 2000 May 1;60(9):2419-28. PubMed PMID: 10811119.

219: Motwani M, Li X, Schwartz GK. Flavopiridol, a cyclin-dependent kinase inhibitor, prevents spindle inhibitor-induced endoreduplication in human cancer cells. Clin Cancer Res. 2000 Mar;6(3):924-32. PubMed PMID: 10741717.

220: Bible KC, Boerner SA, Kirkland K, Anderl KL, Bartelt D Jr, Svingen PA, Kottke TJ, Lee YK, Eckdahl S, Stalboerger PG, Jenkins RB, Kaufmann SH. Characterization of an ovarian carcinoma cell line resistant to cisplatin and flavopiridol. Clin Cancer Res. 2000 Feb;6(2):661-70. PubMed PMID: 10690552.

221: Senderowicz AM. Flavopiridol: the first cyclin-dependent kinase inhibitor in human clinical trials. Invest New Drugs. 1999;17(3):313-20. Review. PubMed PMID: 10665481.

222: Li Y, Bhuiyan M, Alhasan S, Senderowicz AM, Sarkar FH. Induction of apoptosis and inhibition of c-erbB-2 in breast cancer cells by flavopiridol. Clin Cancer Res. 2000 Jan;6(1):223-9. PubMed PMID: 10656453.

223: Stadler WM, Vogelzang NJ, Amato R, Sosman J, Taber D, Liebowitz D, Vokes EE. Flavopiridol, a novel cyclin-dependent kinase inhibitor, in metastatic renal cancer: a University of Chicago Phase II Consortium study. J Clin Oncol. 2000 Jan;18(2):371-5. PubMed PMID: 10637252.

224: Melillo G, Sausville EA, Cloud K, Lahusen T, Varesio L, Senderowicz AM. Flavopiridol, a protein kinase inhibitor, down-regulates hypoxic induction of vascular endothelial growth factor expression in human monocytes. Cancer Res. 1999 Nov 1;59(21):5433-7. PubMed PMID: 10554012.

225: Shapiro GI, Koestner DA, Matranga CB, Rollins BJ. Flavopiridol induces cell cycle arrest and p53-independent apoptosis in non-small cell lung cancer cell lines. Clin Cancer Res. 1999 Oct;5(10):2925-38. PubMed PMID: 10537362.

226: Hooijberg JH, Broxterman HJ, Scheffer GL, Vrasdonk C, Heijn M, de Jong MC, Scheper RJ, Lankelma J, Pinedo HM. Potent interaction of flavopiridol with MRP1. Br J Cancer. 1999 Sep;81(2):269-76. PubMed PMID: 10496352; PubMed Central PMCID: PMC2362861.

227: Carlson B, Lahusen T, Singh S, Loaiza-Perez A, Worland PJ, Pestell R, Albanese C, Sausville EA, Senderowicz AM. Down-regulation of cyclin D1 by transcriptional repression in MCF-7 human breast carcinoma cells induced by flavopiridol. Cancer Res. 1999 Sep 15;59(18):4634-41. PubMed PMID: 10493518.

228: Li P, Tabibi SE, Yalkowsky SH. Solubilization of flavopiridol by pH control combined with cosolvents, surfactants, or complexants. J Pharm Sci. 1999 Sep;88(9):945-7. PubMed PMID: 10479359.

229: Ruef J, Meshel AS, Hu Z, Horaist C, Ballinger CA, Thompson LJ, Subbarao VD, Dumont JA, Patterson C. Flavopiridol inhibits smooth muscle cell proliferation in vitro and neointimal formation In vivo after carotid injury in the rat. Circulation. 1999 Aug 10;100(6):659-65. PubMed PMID: 10441105.

230: Motwani M, Delohery TM, Schwartz GK. Sequential dependent enhancement of caspase activation and apoptosis by flavopiridol on paclitaxel-treated human gastric and breast cancer cells. Clin Cancer Res. 1999 Jul;5(7):1876-83. PubMed PMID: 10430095.

231: Schnier JB, Kaur G, Kaiser A, Stinson SF, Sausville EA, Gardner J, Nishi K, Bradbury EM, Senderowicz AM. Identification of cytosolic aldehyde dehydrogenase 1 from non-small cell lung carcinomas as a flavopiridol-binding protein. FEBS Lett. 1999 Jul 2;454(1-2):100-4. PubMed PMID: 10413104.

232: Chien M, Astumian M, Liebowitz D, Rinker-Schaeffer C, Stadler WM. In vitro evaluation of flavopiridol, a novel cell cycle inhibitor, in bladder cancer. Cancer Chemother Pharmacol. 1999;44(1):81-7. PubMed PMID: 10367753.

233: Li P, Tabibi SE, Yalkowsky SH. Solubilization of ionized and un-ionized flavopiridol by ethanol and polysorbate 20. J Pharm Sci. 1999 May;88(5):507-9. PubMed PMID: 10229640.

234: Schrump DS, Matthews W, Chen GA, Mixon A, Altorki NK. Flavopiridol mediates cell cycle arrest and apoptosis in esophageal cancer cells. Clin Cancer Res. 1998 Nov;4(11):2885-90. PubMed PMID: 9829756.

235: Schwartz GK, Farsi K, Maslak P, Kelsen DP, Spriggs D. Potentiation of apoptosis by flavopiridol in mitomycin-C-treated gastric and breast cancer cells. Clin Cancer Res. 1997 Sep;3(9):1467-72. PubMed PMID: 9815832.

236: Byrd JC, Shinn C, Waselenko JK, Fuchs EJ, Lehman TA, Nguyen PL, Flinn IW, Diehl LF, Sausville E, Grever MR. Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-3 without evidence of bcl-2 modulation or dependence on functional p53. Blood. 1998 Nov 15;92(10):3804-16. PubMed PMID: 9808574.

237: Patel V, Senderowicz AM, Pinto D Jr, Igishi T, Raffeld M, Quintanilla-Martinez L, Ensley JF, Sausville EA, Gutkind JS. Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis. J Clin Invest. 1998 Nov 1;102(9):1674-81. PubMed PMID: 9802881; PubMed Central PMCID: PMC509115.

238: Moorthamer M, Panchal M, Greenhalf W, Chaudhuri B. The p16(INK4A) protein and flavopiridol restore yeast cell growth inhibited by Cdk4. Biochem Biophys Res Commun. 1998 Sep 29;250(3):791-7. PubMed PMID: 9784425.

239: Stinson SF, Hill K, Siford TJ, Phillips LR, Daw TW. Determination of flavopiridol (L86 8275; NSC 649890) in human plasma by reversed-phase liquid chromatography with electrochemical detection. Cancer Chemother Pharmacol. 1998;42(4):261-5. PubMed PMID: 9744769.

240: Senderowicz AM, Headlee D, Stinson SF, Lush RM, Kalil N, Villalba L, Hill K, Steinberg SM, Figg WD, Tompkins A, Arbuck SG, Sausville EA. Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms. J Clin Oncol. 1998 Sep;16(9):2986-99. PubMed PMID: 9738567.

241: Wright J, Blatner GL, Cheson BD. Clinical trials referral resource. Clinical trials of flavopiridol. Oncology (Williston Park). 1998 Jul;12(7):1018, 1023-4. PubMed PMID: 9684276.

242: Brüsselbach S, Nettelbeck DM, Sedlacek HH, Müller R. Cell cycle-independent induction of apoptosis by the anti-tumor drug Flavopiridol in endothelial cells. Int J Cancer. 1998 Jul 3;77(1):146-52. PubMed PMID: 9639406.

243: Jäger W, Zembsch B, Wolschann P, Pittenauer E, Senderowicz AM, Sausville EA, Sedlacek HH, Graf J, Thalhammer T. Metabolism of the anticancer drug flavopiridol, a new inhibitor of cyclin dependent kinases, in rat liver. Life Sci. 1998;62(20):1861-73. PubMed PMID: 9600328.

244: Arguello F, Alexander M, Sterry JA, Tudor G, Smith EM, Kalavar NT, Greene JF Jr, Koss W, Morgan CD, Stinson SF, Siford TJ, Alvord WG, Klabansky RL, Sausville EA. Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity In vivo against human leukemia and lymphoma xenografts. Blood. 1998 Apr 1;91(7):2482-90. PubMed PMID: 9516149.

245: Parker BW, Kaur G, Nieves-Neira W, Taimi M, Kohlhagen G, Shimizu T, Losiewicz MD, Pommier Y, Sausville EA, Senderowicz AM. Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol. Blood. 1998 Jan 15;91(2):458-65. PubMed PMID: 9427698.

246: König A, Schwartz GK, Mohammad RM, Al-Katib A, Gabrilove JL. The novel cyclin-dependent kinase inhibitor flavopiridol downregulates Bcl-2 and induces growth arrest and apoptosis in chronic B-cell leukemia lines. Blood. 1997 Dec 1;90(11):4307-12. PubMed PMID: 9373241.

247: Bible KC, Kaufmann SH. Cytotoxic synergy between flavopiridol (NSC 649890, L86-8275) and various antineoplastic agents: the importance of sequence of administration. Cancer Res. 1997 Aug 15;57(16):3375-80. PubMed PMID: 9269999.

248: Drees M, Dengler WA, Roth T, Labonte H, Mayo J, Malspeis L, Grever M, Sausville EA, Fiebig HH. Flavopiridol (L86-8275): selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells. Clin Cancer Res. 1997 Feb;3(2):273-9. PubMed PMID: 9815683.

249: Sedlacek H, Czech J, Naik R, Kaur G, Worland P, Losiewicz M, Parker B, Carlson B, Smith A, Senderowicz A, Sausville E. Flavopiridol (L86 8275; NSC 649890), a new kinase inhibitor for tumor therapy. Int J Oncol. 1996 Dec;9(6):1143-68. PubMed PMID: 21541623.

250: Dannenfelser RM, Surakitbanharn Y, Tabibi SE, Yalkowsky SH. Parenteral formulation of Flavopiridol (NSC-649890). PDA J Pharm Sci Technol. 1996 Nov-Dec;50(6):356-9. PubMed PMID: 9038080.

251: Bible KC, Kaufmann SH. Flavopiridol: a cytotoxic flavone that induces cell death in noncycling A549 human lung carcinoma cells. Cancer Res. 1996 Nov 1;56(21):4856-61. PubMed PMID: 8895733.

252: Carlson BA, Dubay MM, Sausville EA, Brizuela L, Worland PJ. Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. Cancer Res. 1996 Jul 1;56(13):2973-8. PubMed PMID: 8674031.