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Entinostat

Description of Entinostat: Entinostat is a synthetic benzamide derivative with potential antineoplastic activity. Entinostat binds to and inhibits histone deacetylase, an enzyme that regulates chromatin structure and gene transcription. This agent appears to exert dose-dependent effects in human leukemia cells including cyclin-dependent kinase inhibitor 1A (p21/CIP1/WAF1)-dependent growth arrest and differentiation at low drug concentrations; a marked induction of reactive oxygen species (ROS); mitochondrial damage; caspase activation; and, at higher concentrations, apoptosis. In normal cells, cyclin-dependent kinase inhibitor 1A expression has been associated with cell-cycle exit and differentiation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:  Syndax Pharmaceuticals Inc.

Entinostat inhibits class I HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM, respectively.  Entinostat  preferentially inhibits cell proliferation/survival and inactivates downstream signaling in erbB2-overexpressing compared with basal breast cancer cells. Entinostat  reduces the levels of both erbB2 and erbB3, as well as significantly decreases P-erbB2, P-erbB3, P-Akt, and P-MAPK in erbB2-overexpressing cells. Additionally, Entinostat promotes apoptosis and induces cell cycle arrest predominantly at G(1) phase in erbB2-overexpressing cells, whereas Entinostat  mainly induces G(2)-M arrest in basal breast cancer cells. The cellular bias of Entinostat  is shown to be related partly to the levels of erbB3 expression that directly impact the ability of Entinostat  to inhibit proliferation/survival of the erbB2-overexpressing breast cancer cells. These findings show that Entinostat may be developed as a novel therapeutic agent to treat breast cancers with coexpression of both erbB2 and erbB3. see http://www.ncbi.nlm.nih.gov/pubmed/19826038.

Entinostat is an orally bioavailable, selective, class I histone deacetylase (HDAC) inhibitor. Entinostat is currently being investigated in randomized, Phase 2 clinical studies in combination with the aromatase inhibitor, exemestane, for the treatment of metastatic or locally advanced ER+ breast cancer; in combination with erlotinib in advanced non-small-cell lung cancer, and in combination with azacitidine in myelodysplastic syndrome. Phase 2 single arm studies in non-small cell lung cancer and colorectal cancer, also are being conducted in combination with azacitidine; and a Phase 2 in Hodgkin's lymphoma is ongoing with single agent entinostat. Entinostat's long half-life allows for weekly or every-other-week oral dosing.

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2: Kakihana M, Ohira T, Chan D, Webster RB, Kato H, Drabkin HA, Gemmill RM. Induction of E-cadherin in lung cancer and interaction with growth suppression by histone deacetylase inhibition. J Thorac Oncol. 2009 Dec;4(12):1455-65. PubMed PMID: 20009910; PubMed Central PMCID: PMC2796578.

3: Purrucker JC, Fricke A, Ong MF, Rübe C, Rübe CE, Mahlknecht U. HDAC inhibition radiosensitizes human normal tissue cells and reduces DNA Double-Strand Break repair capacity. Oncol Rep. 2010 Jan;23(1):263-9. PubMed PMID: 19956891.

4: Flis S, Gnyszka A, Flis K, Spławiński J. MS275 enhances cytotoxicity induced by 5-fluorouracil in the colorectal cancer cells. Eur J Pharmacol. 2010 Feb 10;627(1-3):26-32. Epub 2009 Oct 22. PubMed PMID: 19853597.

5: Huang X, Gao L, Wang S, Lee CK, Ordentlich P, Liu B. HDAC inhibitor SNDX-275 induces apoptosis in erbB2-overexpressing breast cancer cells via down-regulation of erbB3 expression. Cancer Res. 2009 Nov 1;69(21):8403-11. Epub 2009 Oct 13. PubMed PMID: 19826038.

6: Borbone E, Berlingieri MT, De Bellis F, Nebbioso A, Chiappetta G, Mai A, Altucci L, Fusco A. Histone deacetylase inhibitors induce thyroid cancer-specific apoptosis through proteasome-dependent inhibition of TRAIL degradation. Oncogene. 2010 Jan 7;29(1):105-16. Epub 2009 Oct 5. PubMed PMID: 19802013.

7: Vire B, de Walque S, Restouin A, Olive D, Van Lint C, Collette Y. Anti-leukemia activity of MS-275 histone deacetylase inhibitor implicates 4-1BBL/4-1BB immunomodulatory functions. PLoS One. 2009 Sep 17;4(9):e7085. PubMed PMID: 19759901; PubMed Central PMCID: PMC2738963.

8: Covington HE 3rd, Maze I, LaPlant QC, Vialou VF, Ohnishi YN, Berton O, Fass DM, Renthal W, Rush AJ 3rd, Wu EY, Ghose S, Krishnan V, Russo SJ, Tamminga C, Haggarty SJ, Nestler EJ. Antidepressant actions of histone deacetylase inhibitors. J Neurosci. 2009 Sep 16;29(37):11451-60. PubMed PMID: 19759294; PubMed Central PMCID: PMC2775805.

9: Bracker TU, Sommer A, Fichtner I, Faus H, Haendler B, Hess-Stumpp H. Efficacy of MS-275, a selective inhibitor of class I histone deacetylases, in human colon cancer models. Int J Oncol. 2009 Oct;35(4):909-20. PubMed PMID: 19724929.

10: Li Q, Bartlett DL, Gorry MC, O'Malley ME, Guo ZS. Three epigenetic drugs up-regulate homeobox gene Rhox5 in cancer cells through overlapping and distinct molecular mechanisms. Mol Pharmacol. 2009 Nov;76(5):1072-81. Epub 2009 Aug 13. PubMed PMID: 19679824.

11: Figueroa ME, Skrabanek L, Li Y, Jiemjit A, Fandy TE, Paietta E, Fernandez H, Tallman MS, Greally JM, Carraway H, Licht JD, Gore SD, Melnick A. MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation. Blood. 2009 Oct 15;114(16):3448-58. Epub 2009 Aug 3. PubMed PMID: 19652201; PubMed Central PMCID: PMC2765680.

12: Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. Epub 2009 Jul 16. PubMed PMID: 19608861.

13: Häcker S, Dittrich A, Mohr A, Schweitzer T, Rutkowski S, Krauss J, Debatin KM, Fulda S. Histone deacetylase inhibitors cooperate with IFN-gamma to restore caspase-8 expression and overcome TRAIL resistance in cancers with silencing of caspase-8. Oncogene. 2009 Sep 3;28(35):3097-110. Epub 2009 Jul 13. PubMed PMID: 19597472.

14: Flis S, Gnyszka A, Spławiński J. HDAC inhibitors, MS275 and SBHA, enhances cytotoxicity induced by oxaliplatin in the colorectal cancer cell lines. Biochem Biophys Res Commun. 2009 Sep 18;387(2):336-41. Epub 2009 Jul 9. PubMed PMID: 19596269.

15: Fandy TE, Herman JG, Kerns P, Jiemjit A, Sugar EA, Choi SH, Yang AS, Aucott T, Dauses T, Odchimar-Reissig R, Licht J, McConnell MJ, Nasrallah C, Kim MK, Zhang W, Sun Y, Murgo A, Espinoza-Delgado I, Oteiza K, Owoeye I, Silverman LR, Gore SD, Carraway HE. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. Blood. 2009 Sep 24;114(13):2764-73. Epub 2009 Jun 22. PubMed PMID: 19546476; PubMed Central PMCID: PMC2756131.

16: Sun P, Xia S, Lal B, Eberhart CG, Quinones-Hinojosa A, Maciaczyk J, Matsui W, Dimeco F, Piccirillo SM, Vescovi AL, Laterra J. DNER, an epigenetically modulated gene, regulates glioblastoma-derived neurosphere cell differentiation and tumor propagation. Stem Cells. 2009 Jul;27(7):1473-86. PubMed PMID: 19544453.

17: Prince HM, Bishton MJ, Harrison SJ. Clinical studies of histone deacetylase inhibitors. Clin Cancer Res. 2009 Jun 15;15(12):3958-69. Epub 2009 Jun 9. Review. PubMed PMID: 19509172.

18: Piekarz RL, Bates SE. Epigenetic modifiers: basic understanding and clinical development. Clin Cancer Res. 2009 Jun 15;15(12):3918-26. Epub 2009 Jun 9. PubMed PMID: 19509169.

19: Gaymes TJ, Shall S, MacPherson LJ, Twine NA, Lea NC, Farzaneh F, Mufti GJ. Inhibitors of poly ADP-ribose polymerase (PARP) induce apoptosis of myeloid leukemic cells: potential for therapy of myeloid leukemia and myelodysplastic syndromes. Haematologica. 2009 May;94(5):638-46. PubMed PMID: 19407318; PubMed Central PMCID: PMC2675675.

20: Lucas JL, Mirshahpanah P, Haas-Stapleton E, Asadullah K, Zollner TM, Numerof RP. Induction of Foxp3+ regulatory T cells with histone deacetylase inhibitors. Cell Immunol. 2009;257(1-2):97-104. Epub 2009 Apr 8. PubMed PMID: 19358983.

21: Slattery EL, Speck JD, Warchol ME. Epigenetic influences on sensory regeneration: histone deacetylases regulate supporting cell proliferation in the avian utricle. J Assoc Res Otolaryngol. 2009 Sep;10(3):341-53. Epub 2009 Apr 2. PubMed PMID: 19340485.

22: Chiechio S, Zammataro M, Morales ME, Busceti CL, Drago F, Gereau RW 4th, Copani A, Nicoletti F. Epigenetic modulation of mGlu2 receptors by histone deacetylase inhibitors in the treatment of inflammatory pain. Mol Pharmacol. 2009 May;75(5):1014-20. Epub 2009 Mar 2. PubMed PMID: 19255242.

23: Niesen MI, Blanck G. Rescue of major histocompatibility-DR surface expression in retinoblastoma-defective, non-small cell lung carcinoma cells by the MS-275 histone deacetylase inhibitor. Biol Pharm Bull. 2009 Mar;32(3):480-2. PubMed PMID: 19252299.

24: Aguilera DG, Das CM, Sinnappah-Kang ND, Joyce C, Taylor PH, Wen S, Hasselblatt M, Paulus W, Fuller G, Wolff JE, Gopalakrishnan V. Reactivation of death receptor 4 (DR4) expression sensitizes medulloblastoma cell lines to TRAIL. J Neurooncol. 2009 Jul;93(3):303-18. Epub 2009 Jan 16. PubMed PMID: 19148581.

25: Danish M, Gardner ER, Chen X, Figg WD. Determination of a benzamide histone deacetylase inhibitor, MS-275, in human plasma by liquid chromatography with mass-spectrometric detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jan 15;877(3):355-9. Epub 2008 Dec 13. PubMed PMID: 19117815; PubMed Central PMCID: PMC2661872.

26: Colussi C, Mozzetta C, Gurtner A, Illi B, Rosati J, Straino S, Ragone G, Pescatori M, Zaccagnini G, Antonini A, Minetti G, Martelli F, Piaggio G, Gallinari P, Steinkuhler C, Clementi E, Dell'Aversana C, Altucci L, Mai A, Capogrossi MC, Puri PL, Gaetano C. HDAC2 blockade by nitric oxide and histone deacetylase inhibitors reveals a common target in Duchenne muscular dystrophy treatment. Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19183-7. Epub 2008 Dec 1. Erratum in: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1679. Steinkulher, Christian [corrected to Steinkuhler, Christian]. PubMed PMID: 19047631; PubMed Central PMCID: PMC2614736.

27: Kundakovic M, Chen Y, Guidotti A, Grayson DR. The reelin and GAD67 promoters are activated by epigenetic drugs that facilitate the disruption of local repressor complexes. Mol Pharmacol. 2009 Feb;75(2):342-54. Epub 2008 Nov 24. PubMed PMID: 19029285; PubMed Central PMCID: PMC2684898.

28: Gahr S, Peter G, Wissniowski TT, Hahn EG, Herold C, Ocker M. The histone-deacetylase inhibitor MS-275 and the CDK-inhibitor CYC-202 promote anti-tumor effects in hepatoma cell lines. Oncol Rep. 2008 Nov;20(5):1249-56. PubMed PMID: 18949429.

29: Prasad P, Vasquez H, Das CM, Gopalakrishnan V, Wolff JE. Histone acetylation resulting in resistance to methotrexate in choroid plexus cells. J Neurooncol. 2009 Feb;91(3):279-86. Epub 2008 Oct 14. PubMed PMID: 18853233.

30: Nguyên TL, Abdelbary H, Arguello M, Breitbach C, Leveille S, Diallo JS, Yasmeen A, Bismar TA, Kirn D, Falls T, Snoulten VE, Vanderhyden BC, Werier J, Atkins H, Vähä-Koskela MJ, Stojdl DF, Bell JC, Hiscott J. Chemical targeting of the innate antiviral response by histone deacetylase inhibitors renders refractory cancers sensitive to viral oncolysis. Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14981-6. Epub 2008 Sep 24. PubMed PMID: 18815361; PubMed Central PMCID: PMC2567479.

31: Björkman M, Iljin K, Halonen P, Sara H, Kaivanto E, Nees M, Kallioniemi OP. Defining the molecular action of HDAC inhibitors and synergism with androgen deprivation in ERG-positive prostate cancer. Int J Cancer. 2008 Dec 15;123(12):2774-81. PubMed PMID: 18798265.

32: Nishioka C, Ikezoe T, Yang J, Koeffler HP, Yokoyama A. Blockade of mTOR signaling potentiates the ability of histone deacetylase inhibitor to induce growth arrest and differentiation of acute myelogenous leukemia cells. Leukemia. 2008 Dec;22(12):2159-68. Epub 2008 Sep 11. PubMed PMID: 18784743.

33: Xu J, Zhou JY, Wei WZ, Philipsen S, Wu GS. Sp1-mediated TRAIL induction in chemosensitization. Cancer Res. 2008 Aug 15;68(16):6718-26. PubMed PMID: 18701496; PubMed Central PMCID: PMC2631399.

34: Di Bernardo G, Squillaro T, Dell'Aversana C, Miceli M, Cipollaro M, Cascino A, Altucci L, Galderisi U. Histone deacetylase inhibitors promote apoptosis and senescence in human mesenchymal stem cells. Stem Cells Dev. 2009 May;18(4):573-81. PubMed PMID: 18694296.

35: Chen T, Lee MJ, Kim YS, Lee S, Kummar S, Gutierrez M, Hewitt SM, Trepel JB, Levin IW. Pharmacodynamic assessment of histone deacetylase inhibitors: infrared vibrational spectroscopic imaging of protein acetylation. Anal Chem. 2008 Aug 15;80(16):6390-6. Epub 2008 Jul 24. PubMed PMID: 18651756; PubMed Central PMCID: PMC2684873.

36: Hauschild A, Trefzer U, Garbe C, Kaehler KC, Ugurel S, Kiecker F, Eigentler T, Krissel H, Schott A, Schadendorf D. Multicenter phase II trial of the histone deacetylase inhibitor pyridylmethyl-N-{4-[(2-aminophenyl)-carbamoyl]-benzyl}-carbamate in pretreated metastatic melanoma. Melanoma Res. 2008 Aug;18(4):274-8. PubMed PMID: 18626312.

37: Gore L, Rothenberg ML, O'Bryant CL, Schultz MK, Sandler AB, Coffin D, McCoy C, Schott A, Scholz C, Eckhardt SG. A phase I and pharmacokinetic study of the oral histone deacetylase inhibitor, MS-275, in patients with refractory solid tumors and lymphomas. Clin Cancer Res. 2008 Jul 15;14(14):4517-25. Epub 2008 Jun 25. PubMed PMID: 18579665; PubMed Central PMCID: PMC2813676.

38: Liu S, Cheng H, Kwan W, Lubieniecka JM, Nielsen TO. Histone deacetylase inhibitors induce growth arrest, apoptosis, and differentiation in clear cell sarcoma models. Mol Cancer Ther. 2008 Jun;7(6):1751-61. PubMed PMID: 18566246.

39: Dalgard CL, Van Quill KR, O'Brien JM. Evaluation of the in vitro and in vivo antitumor activity of histone deacetylase inhibitors for the therapy of retinoblastoma. Clin Cancer Res. 2008 May 15;14(10):3113-23. PubMed PMID: 18483379.

40: Nishioka C, Ikezoe T, Yang J, Takeuchi S, Koeffler HP, Yokoyama A. MS-275, a novel histone deacetylase inhibitor with selectivity against HDAC1, induces degradation of FLT3 via inhibition of chaperone function of heat shock protein 90 in AML cells. Leuk Res. 2008 Sep;32(9):1382-92. Epub 2008 Apr 3. PubMed PMID: 18394702.

41: Rasheed W, Bishton M, Johnstone RW, Prince HM. Histone deacetylase inhibitors in lymphoma and solid malignancies. Expert Rev Anticancer Ther. 2008 Mar;8(3):413-32. Review. PubMed PMID: 18366289.

42: Khandelwal A, Gediya L, Njar V. MS-275 synergistically enhances the growth inhibitory effects of RAMBA VN/66-1 in hormone-insensitive PC-3 prostate cancer cells and tumours. Br J Cancer. 2008 Apr 8;98(7):1234-43. Epub 2008 Mar 18. PubMed PMID: 18349838; PubMed Central PMCID: PMC2359640.

43: Jones P, Altamura S, De Francesco R, Gallinari P, Lahm A, Neddermann P, Rowley M, Serafini S, Steinkühler C. Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases. Bioorg Med Chem Lett. 2008 Mar 15;18(6):1814-9. Epub 2008 Feb 14. PubMed PMID: 18308563.

44: Nishioka C, Ikezoe T, Yang J, Koeffler HP, Yokoyama A. Inhibition of MEK/ERK signaling synergistically potentiates histone deacetylase inhibitor-induced growth arrest, apoptosis and acetylation of histone H3 on p21waf1 promoter in acute myelogenous leukemia cell. Leukemia. 2008 Jul;22(7):1449-52. Epub 2008 Jan 10. PubMed PMID: 18185526.

45: Gediya LK, Belosay A, Khandelwal A, Purushottamachar P, Njar VC. Improved synthesis of histone deacetylase inhibitors (HDIs) (MS-275 and CI-994) and inhibitory effects of HDIs alone or in combination with RAMBAs or retinoids on growth of human LNCaP prostate cancer cells and tumor xenografts. Bioorg Med Chem. 2008 Mar 15;16(6):3352-60. Epub 2007 Dec 8. PubMed PMID: 18166465; PubMed Central PMCID: PMC2374748.

46: Chen YD, Jiang YJ, Zhou JW, Yu QS, You QD. Identification of ligand features essential for HDACs inhibitors by pharmacophore modeling. J Mol Graph Model. 2008 Apr;26(7):1160-8. Epub 2007 Oct 23. PubMed PMID: 18061500.

47: Gao S, Mobley A, Miller C, Boklan J, Chandra J. Potentiation of reactive oxygen species is a marker for synergistic cytotoxicity of MS-275 and 5-azacytidine in leukemic cells. Leuk Res. 2008 May;32(5):771-80. Epub 2007 Nov 26. PubMed PMID: 18031811; PubMed Central PMCID: PMC2320596.

48: Charrier C, Roche J, Gesson JP, Bertrand P. Antiproliferative activities of a library of hybrids between indanones and HDAC inhibitor SAHA and MS-275 analogues. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6142-6. Epub 2007 Sep 14. PubMed PMID: 17897824.

49: Horita H, Frankel AE, Thorburn A. Acute-myeloid-leukemia-targeted toxins kill tumor cells by cell-type-specific mechanisms and synergize with TRAIL to allow manipulation of the extent and mechanism of tumor cell death. Leukemia. 2008 Mar;22(3):652-5. Epub 2007 Sep 20. PubMed PMID: 17882279.

50: Kummar S, Gutierrez M, Gardner ER, Donovan E, Hwang K, Chung EJ, Lee MJ, Maynard K, Kalnitskiy M, Chen A, Melillo G, Ryan QC, Conley B, Figg WD, Trepel JB, Zwiebel J, Doroshow JH, Murgo AJ. Phase I trial of MS-275, a histone deacetylase inhibitor, administered weekly in refractory solid tumors and lymphoid malignancies. Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5411-7. PubMed PMID: 17875771.

51: Baradari V, Höpfner M, Huether A, Schuppan D, Scherübl H. Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells. World J Gastroenterol. 2007 Sep 7;13(33):4458-66. PubMed PMID: 17724801.

52: Kato Y, Yoshimura K, Shin T, Verheul H, Hammers H, Sanni TB, Salumbides BC, Van Erp K, Schulick R, Pili R. Synergistic in vivo antitumor effect of the histone deacetylase inhibitor MS-275 in combination with interleukin 2 in a murine model of renal cell carcinoma. Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4538-46. PubMed PMID: 17671140.

53: Nishioka C, Ikezoe T, Yang J, Komatsu N, Bandobashi K, Taniguchi A, Kuwayama Y, Togitani K, Koeffler HP, Taguchi H. Histone deacetylase inhibitors induce growth arrest and apoptosis of HTLV-1-infected T-cells via blockade of signaling by nuclear factor kappaB. Leuk Res. 2008 Feb;32(2):287-96. Epub 2007 Jul 20. PubMed PMID: 17644177.

54: Nencioni A, Beck J, Werth D, Grünebach F, Patrone F, Ballestrero A, Brossart P. Histone deacetylase inhibitors affect dendritic cell differentiation and immunogenicity. Clin Cancer Res. 2007 Jul 1;13(13):3933-41. PubMed PMID: 17606727.

55: Haffner I, Teupser D, Holdt LM, Ernst J, Burkhardt R, Thiery J. Regulation of arginase-1 expression in macrophages by a protein kinase A type I and histone deacetylase dependent pathway. J Cell Biochem. 2008 Feb 1;103(2):520-7. PubMed PMID: 17577214.

56: Qian DZ, Wei YF, Wang X, Kato Y, Cheng L, Pili R. Antitumor activity of the histone deacetylase inhibitor MS-275 in prostate cancer models. Prostate. 2007 Aug 1;67(11):1182-93. PubMed PMID: 17520666.

57: Di Renzo F, Broccia ML, Giavini E, Menegola E. Relationship between embryonic histonic hyperacetylation and axial skeletal defects in mouse exposed to the three HDAC inhibitors apicidin, MS-275, and sodium butyrate. Toxicol Sci. 2007 Aug;98(2):582-8. Epub 2007 May 21. PubMed PMID: 17517827.

58: Tsapis M, Lieb M, Manzo F, Shankaranarayanan P, Herbrecht R, Lutz P, Gronemeyer H. HDAC inhibitors induce apoptosis in glucocorticoid-resistant acute lymphatic leukemia cells despite a switch from the extrinsic to the intrinsic death pathway. Int J Biochem Cell Biol. 2007;39(7-8):1500-9. Epub 2007 Mar 15. PubMed PMID: 17499001.

59: Sonnemann J, Dreyer L, Hartwig M, Palani CD, Hong le TT, Klier U, Bröker B, Völker U, Beck JF. Histone deacetylase inhibitors induce cell death and enhance the apoptosis-inducing activity of TRAIL in Ewing's sarcoma cells. J Cancer Res Clin Oncol. 2007 Nov;133(11):847-58. Epub 2007 May 8. PubMed PMID: 17486365.

60: Hess-Stumpp H, Bracker TU, Henderson D, Politz O. MS-275, a potent orally available inhibitor of histone deacetylases--the development of an anticancer agent. Int J Biochem Cell Biol. 2007;39(7-8):1388-405. Epub 2007 Feb 16. Review. PubMed PMID: 17383217.

61: Zhang M, Aguilera D, Das C, Vasquez H, Zage P, Gopalakrishnan V, Wolff J. Measuring cytotoxicity: a new perspective on LC50. Anticancer Res. 2007 Jan-Feb;27(1A):35-8. PubMed PMID: 17352213.

62: Lin HS, Hu CY, Chan HY, Liew YY, Huang HP, Lepescheux L, Bastianelli E, Baron R, Rawadi G, Clément-Lacroix P. Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents. Br J Pharmacol. 2007 Apr;150(7):862-72. Epub 2007 Feb 26. PubMed PMID: 17325656; PubMed Central PMCID: PMC2013883.

63: Picard V, Bergeron A, Larue H, Fradet Y. MAGE-A9 mRNA and protein expression in bladder cancer. Int J Cancer. 2007 May 15;120(10):2170-7. PubMed PMID: 17290406.

64: Kasman L, Lu P, Voelkel-Johnson C. The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells. Cancer Gene Ther. 2007 Mar;14(3):327-34. Epub 2006 Dec 22. PubMed PMID: 17186014.

65: Gojo I, Jiemjit A, Trepel JB, Sparreboom A, Figg WD, Rollins S, Tidwell ML, Greer J, Chung EJ, Lee MJ, Gore SD, Sausville EA, Zwiebel J, Karp JE. Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias. Blood. 2007 Apr 1;109(7):2781-90. PubMed PMID: 17179232; PubMed Central PMCID: PMC1852211.

66: Baradari V, Huether A, Höpfner M, Schuppan D, Scherübl H. Antiproliferative and proapoptotic effects of histone deacetylase inhibitors on gastrointestinal neuroendocrine tumor cells. Endocr Relat Cancer. 2006 Dec;13(4):1237-50. PubMed PMID: 17158768.

67: Zhao M, Rudek MA, Mnasakanyan A, Hartke C, Pili R, Baker SD. A liquid chromatography/tandem mass spectrometry assay to quantitate MS-275 in human plasma. J Pharm Biomed Anal. 2007 Jan 17;43(2):784-7. Epub 2006 Sep 12. PubMed PMID: 16971082; PubMed Central PMCID: PMC1797151.

68: Fouladi M. Histone deacetylase inhibitors in cancer therapy. Cancer Invest. 2006 Aug-Sep;24(5):521-7. Review. PubMed PMID: 16939962.

69: Marcu MG, Jung YJ, Lee S, Chung EJ, Lee MJ, Trepel J, Neckers L. Curcumin is an inhibitor of p300 histone acetylatransferase. Med Chem. 2006 Mar;2(2):169-74. PubMed PMID: 16787365.

70: Hölsken A, Eyüpoglu IY, Lueders M, Tränkle C, Dieckmann D, Buslei R, Hahnen E, Blümcke I, Siebzehnrübl FA. Ex vivo therapy of malignant melanomas transplanted into organotypic brain slice cultures using inhibitors of histone deacetylases. Acta Neuropathol. 2006 Aug;112(2):205-15. Epub 2006 Jun 14. PubMed PMID: 16773328.

71: Eyüpoglu IY, Hahnen E, Tränkle C, Savaskan NE, Siebzehnrübl FA, Buslei R, Lemke D, Wick W, Fahlbusch R, Blümcke I. Experimental therapy of malignant gliomas using the inhibitor of histone deacetylase MS-275. Mol Cancer Ther. 2006 May;5(5):1248-55. PubMed PMID: 16731757.

72: Moody TW, Nakagawa T, Kang Y, Jakowlew S, Chan D, Jensen RT. Bombesin/gastrin-releasing peptide receptor antagonists increase the ability of histone deacetylase inhibitors to reduce lung cancer proliferation. J Mol Neurosci. 2006;28(3):231-8. PubMed PMID: 16691010.

73: Takai N, Ueda T, Nishida M, Nasu K, Narahara H. Anticancer activity of MS-275, a novel histone deacetylase inhibitor, against human endometrial cancer cells. Anticancer Res. 2006 Mar-Apr;26(2A):939-45. PubMed PMID: 16619490.

74: Acharya MR, Karp JE, Sausville EA, Hwang K, Ryan Q, Gojo I, Venitz J, Figg WD, Sparreboom A. Factors affecting the pharmacokinetic profile of MS-275, a novel histone deacetylase inhibitor, in patients with cancer. Invest New Drugs. 2006 Sep;24(5):367-75. PubMed PMID: 16583304.

75: Blum W, Marcucci G. Targeting epigenetic changes in acute myeloid leukemia. Clin Adv Hematol Oncol. 2005 Nov;3(11):855-65, 882. Review. PubMed PMID: 16491631.

76: Simonini MV, Camargo LM, Dong E, Maloku E, Veldic M, Costa E, Guidotti A. The benzamide MS-275 is a potent, long-lasting brain region-selective inhibitor of histone deacetylases. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1587-92. Epub 2006 Jan 23. PubMed PMID: 16432198; PubMed Central PMCID: PMC1360572.

77: Schroeder TM, Westendorf JJ. Histone deacetylase inhibitors promote osteoblast maturation. J Bone Miner Res. 2005 Dec;20(12):2254-63. Epub 2005 Aug 8. PubMed PMID: 16294278.

78: Chung EJ, Lee S, Sausville EA, Ryan Q, Karp JE, Gojo I, Telford WG, Lee MJ, Kong HS, Trepel JB. Histone deacetylase inhibitor pharmacodynamic analysis by multiparameter flow cytometry. Ann Clin Lab Sci. 2005 Autumn;35(4):397-406. PubMed PMID: 16254255.

79: Early clinical data and potential clinical utility of novel histone deacetylase inhibitors in prostate cancer. Clin Prostate Cancer. 2005 Sep;4(2):83-5. PubMed PMID: 16197607.

80: Liu AL, Long J, Wang N, Du GH. [A new target of cancer therapy: advances in the study of histone deacetylase]. Yao Xue Xue Bao. 2005 Jul;40(7):585-90. Review. Chinese. PubMed PMID: 16196262.

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