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Irofulven

irofulven is a semisynthetic sesquiterpene derivative of illudin S, a natural toxin isolated from the fungus Omphalotus illudens. Irofulven alkylates DNA and protein macromolecules, forms adducts, and arrests cells in the S-phase of the cell cycle. This agent requires NADPH-dependent metabolism by alkenal/one oxidoreductase for activity. Irofulven is more active in vitro against tumor cells of epithelial origin and is more resistant to deactivation by p53 loss and MDR1 than other alkylating agents. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Irofulven or 6-hydroxymethylacylfulvene (also known as HMAF of MGI-114) is an antitumor agent. It belongs to the family of drugs called alkylating agents. It inhibits the replication of DNA. Irofulven is an analogue of illudin S, a sesquiterpene toxin found in mushrooms of the genus Omphalotus. The compound was oringally synthesized by Dr. Trevor McMorris (UCSD) and found to have anticancer properties by Dr. Michael J Kelner (UCSD). see: http://en.wikipedia.org/wiki/Irofulven.

Current developer:    MGI PHARMA

  1: McMorris TC, Chimmani R, Alisala K, Staake MD, Banda G, Kelner MJ. Structure-activity studies of urea, carbamate, and sulfonamide derivatives of acylfulvene. J Med Chem. 2010 Feb 11;53(3):1109-16. PubMed PMID: 20067264.

2: Siegel DS, Piizzi G, Piersanti G, Movassaghi M. Enantioselective total synthesis of (-)-acylfulvene and (-)-irofulven. J Org Chem. 2009 Dec 18;74(24):9292-304. PubMed PMID: 19938810; PubMed Central PMCID: PMC2805080.

3: Escargueil AE, Poindessous V, Soares DG, Sarasin A, Cook PR, Larsen AK. Influence of irofulven, a transcription-coupled repair-specific antitumor agent, on RNA polymerase activity, stability and dynamics in living mammalian cells. J Cell Sci. 2008 Apr 15;121(Pt 8):1275-83. PubMed PMID: 18388315.

4: Dings RP, Van Laar ES, Webber J, Zhang Y, Griffin RJ, Waters SJ, MacDonald JR, Mayo KH. Ovarian tumor growth regression using a combination of vascular targeting agents anginex or topomimetic 0118 and the chemotherapeutic irofulven. Cancer Lett. 2008 Jul 8;265(2):270-80. Epub 2008 Apr 1. PubMed PMID: 18378392.

5: Thuret R, Massard C, Gross-Goupil M, Escudier B, Di Palma M, Bossi A, de Crevoisier R, Chauchereau A, Fizazi K. The postchemotherapy PSA surge syndrome. Ann Oncol. 2008 Jul;19(7):1308-11. Epub 2008 Mar 19. PubMed PMID: 18356135.

6: Kelner MJ, McMorris TC, Rojas RJ, Estes LA, Suthipinijtham P. Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model. Cancer Chemother Pharmacol. 2008 Dec;63(1):19-26. Epub 2008 Feb 28. PubMed PMID: 18305940.

7: Kelner MJ, McMorris TC, Rojas RJ, Estes LA, Suthipinijtham P. Synergy of Irofulven in combination with various anti-metabolites, enzyme inhibitors, and miscellaneous agents in MV522 lung carcinoma cells: marked interaction with gemcitabine and 5-fluorouracil. Invest New Drugs. 2008 Oct;26(5):407-15. Epub 2008 Jan 29. PubMed PMID: 18227973.

8: McMorris TC, Chimmani R, Gurram M, Staake MD, Kelner MJ. Synthesis and antitumor activity of amine analogs of irofulven. Bioorg Med Chem Lett. 2007 Dec 15;17(24):6770-2. Epub 2007 Oct 17. PubMed PMID: 17977722.

9: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Jul-Aug;29(6):427-37. PubMed PMID: 17922073.

10: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Jun;29(5):359-73. PubMed PMID: 17805439.

11: Alexandre J, Kahatt C, Bertheault-Cvitkovic F, Faivre S, Shibata S, Hilgers W, Goldwasser F, Lokiec F, Raymond E, Weems G, Shah A, MacDonald JR, Cvitkovic E. A phase I and pharmacokinetic study of irofulven and capecitabine administered every 2 weeks in patients with advanced solid tumors. Invest New Drugs. 2007 Oct;25(5):453-62. Epub 2007 Jul 13. PubMed PMID: 17628744.

12: Wiltshire T, Senft J, Wang Y, Konat GW, Wenger SL, Reed E, Wang W. BRCA1 contributes to cell cycle arrest and chemoresistance in response to the anticancer agent irofulven. Mol Pharmacol. 2007 Apr;71(4):1051-60. Epub 2007 Jan 17. PubMed PMID: 17229870.

13: Wang Y, Wiltshire T, Senft J, Wenger SL, Reed E, Wang W. Fanconi anemia D2 protein confers chemoresistance in response to the anticancer agent, irofulven. Mol Cancer Ther. 2006 Dec;5(12):3153-61. PubMed PMID: 17172419.

14: Wang Y, Wiltshire T, Senft J, Reed E, Wang W. Irofulven induces replication-dependent CHK2 activation related to p53 status. Biochem Pharmacol. 2007 Feb 15;73(4):469-80. Epub 2006 Oct 27. PubMed PMID: 17118344; PubMed Central PMCID: PMC1800887.

15: Paci A, Rezai K, Deroussent A, De Valeriola D, Re M, Weill S, Cvitkovic E, Kahatt C, Shah A, Waters S, Weems G, Vassal G, Lokiec F. Pharmacokinetics, metabolism, and routes of excretion of intravenous irofulven in patients with advanced solid tumors. Drug Metab Dispos. 2006 Nov;34(11):1918-26. Epub 2006 Aug 8. PubMed PMID: 16896064.

16: Movassaghi M, Piizzi G, Siegel DS, Piersanti G. Enantioselective total synthesis of (-)-acylfulvene and (-)-irofulven. Angew Chem Int Ed Engl. 2006 Sep 4;45(35):5859-63. PubMed PMID: 16888819.

17: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 Jun;28(5):323-43. PubMed PMID: 16845450.

18: Liang H. Comparison of antitumor activities in tumor xenograft treatment. Contemp Clin Trials. 2007 Feb;28(2):115-9. Epub 2006 May 17. PubMed PMID: 16814615.

19: Yeo W, Boyer M, Chung HC, Ong SY, Lim R, Zee B, Ma B, Lam KC, Mo FK, Ng EK, Ho R, Clarke S, Roh JK, Beale P, Rha SY, Jeung HC, Soo R, Goh BC, Chan AT; Cancer Therapeutics Research Group (CTRG). Irofulven as first line therapy in recurrent or metastatic gastric cancer: a phase II multicenter study by the Cancer Therapeutics Research Group (CTRG). Cancer Chemother Pharmacol. 2007 Feb;59(3):295-300. Epub 2006 Jun 17. PubMed PMID: 16783579.

20: Hilgers W, Faivre S, Chieze S, Alexandre J, Lokiec F, Goldwasser F, Raymond E, Kahatt C, Taamma A, Weems G, MacDonald JR, Misset JL, Cvitkovic E. A phase I and pharmacokinetic study of irofulven and cisplatin administered in a 30-min infusion every two weeks to patients with advanced solid tumors. Invest New Drugs. 2006 Jul;24(4):311-9. PubMed PMID: 16683074.

21: Bomgaars LR, Megason GC, Pullen J, Langevin AM, Dale Weitman S, Hershon L, Kuhn JG, Bernstein M, Blaney SM. Phase I trial of irofulven (MGI 114) in pediatric patients with solid tumors. Pediatr Blood Cancer. 2006 Aug;47(2):163-8. PubMed PMID: 16317728.

22: Urien S, Rezaí K, Lokiec F. Pharmacokinetic modelling of 5-FU production from capecitabine--a population study in 40 adult patients with metastatic cancer. J Pharmacokinet Pharmacodyn. 2005 Dec;32(5-6):817-33. PubMed PMID: 16284918.

23: Seiden MV, Gordon AN, Bodurka DC, Matulonis UA, Penson RT, Reed E, Alberts DS, Weems G, Cullen M, McGuire WP 3rd. A phase II study of irofulven in women with recurrent and heavily pretreated ovarian cancer. Gynecol Oncol. 2006 Apr;101(1):55-61. Epub 2005 Nov 2. PubMed PMID: 16260029.

24: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2005 Sep;27(7):505-22. PubMed PMID: 16258596.

25: Serova M, Calvo F, Lokiec F, Koeppel F, Poindessous V, Larsen AK, Laar ES, Waters SJ, Cvitkovic E, Raymond E. Characterizations of irofulven cytotoxicity in combination with cisplatin and oxaliplatin in human colon, breast, and ovarian cancer cells. Cancer Chemother Pharmacol. 2006 Apr;57(4):491-9. Epub 2005 Aug 2. PubMed PMID: 16075278.

26: Senzer N, Arsenau J, Richards D, Berman B, MacDonald JR, Smith S. Irofulven demonstrates clinical activity against metastatic hormone-refractory prostate cancer in a phase 2 single-agent trial. Am J Clin Oncol. 2005 Feb;28(1):36-42. PubMed PMID: 15685033.

27: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Dec;26(10):801-27. PubMed PMID: 15672123.

28: Lee MS, Gupta N, Penson RT, Loewenstein J, Wepner MS, Seiden MV, Milam AH. Cone damage in patients receiving high-dose irofulven treatment. Arch Ophthalmol. 2005 Jan;123(1):29-34. PubMed PMID: 15642808.

29: Dent P, Grant S. Irofulven: resurgence for alkylating therapy in cancer? Cancer Biol Ther. 2004 Nov;3(11):1143-4. Epub 2004 Nov 12. PubMed PMID: 15640616.

30: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Nov;26(9):723-53. PubMed PMID: 15632957.

31: Melendez RF, Harrison JM, Rowinsky EK, Hammond LA, Fitzsimmons TD. Acute retinal toxicity from the novel anti-tumor agent, Irofulven. Doc Ophthalmol. 2004 May;108(3):249-51. PubMed PMID: 15573949.

32: Raymond E, Kahatt C, Rigolet MH, Sutherland W, Lokiec F, Alexandre J, Tombal B, Elman M, Lee MS, MacDonald JR, Cullen M, Misset JL, Cvitkovic E. Characterization and multiparameter analysis of visual adverse events in irofulven single-agent phase I and II trials. Clin Cancer Res. 2004 Nov 15;10(22):7566-74. Erratum in: Clin Cancer Res. 2005 Feb 15;11(4):1684. PubMed PMID: 15569987.

33: Liang H, Salinas RA, Leal BZ, Kosakowska-Cholody T, Michejda CJ, Waters SJ, Herman TS, Woynarowski JM, Woynarowska BA. Caspase-mediated apoptosis and caspase-independent cell death induced by irofulven in prostate cancer cells. Mol Cancer Ther. 2004 Nov;3(11):1385-96. PubMed PMID: 15542777.

34: Woo MH, Peterson JK, Billups C, Liang H, Bjornsti MA, Houghton PJ. Enhanced antitumor activity of irofulven in combination with irinotecan in pediatric solid tumor xenograft models. Cancer Chemother Pharmacol. 2005 May;55(5):411-9. Epub 2004 Oct 16. PubMed PMID: 15503024.

35: Woynarowski JM, Woynarowska BA, Trevino AV, Salinas R, Herman TS, Waters SJ, Macdonald JR. Cell cycle effects and induction of premitotic apoptosis by irofulven in synchronized cancer cells. Cancer Biol Ther. 2004 Nov;3(11):1137-42; discussion 1143-4. Epub 2004 Nov 9. PubMed PMID: 15467441.

36: van Laar ES, Izbicka E, Weitman S, Medina-Gundrum L, Macdonald JR, Waters SJ. Antitumor activity of irofulven against human ovarian cancer cell lines, human tumor colony-forming units, and xenografts. Int J Gynecol Cancer. 2004 Sep-Oct;14(5):824-31. PubMed PMID: 15361190.

37: Koeppel F, Poindessous V, Lazar V, Raymond E, Sarasin A, Larsen AK. Irofulven cytotoxicity depends on transcription-coupled nucleotide excision repair and is correlated with XPG expression in solid tumor cells. Clin Cancer Res. 2004 Aug 15;10(16):5604-13. PubMed PMID: 15328203.

38: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 May;26(4):295-318. PubMed PMID: 15319808.

39: Sherman CA, Herndon JE 2nd, Watson DM, Green MR; Cancer and Leukemia Group B. A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with relapsed or refractory non-small cell lung cancer. Lung Cancer. 2004 Sep;45(3):387-92. PubMed PMID: 15301880.

40: Wang J, Wiltshire T, Wang Y, Mikell C, Burks J, Cunningham C, Van Laar ES, Waters SJ, Reed E, Wang W. ATM-dependent CHK2 activation induced by anticancer agent, irofulven. J Biol Chem. 2004 Sep 17;279(38):39584-92. Epub 2004 Jul 20. PubMed PMID: 15269203.

41: Alexandre J, Raymond E, Kaci MO, Brain EC, Lokiec F, Kahatt C, Faivre S, Yovine A, Goldwasser F, Smith SL, MacDonald JR, Misset JL, Cvitkovic E. Phase I and pharmacokinetic study of irofulven administered weekly or biweekly in advanced solid tumor patients. Clin Cancer Res. 2004 May 15;10(10):3377-85. PubMed PMID: 15161692.

42: Schilder RJ, Blessing JA, Pearl ML, Rose PG. Evaluation of irofulven (MGI-114) in the treatment of recurrent or persistent endometrial carcinoma: A phase II study of the Gynecologic Oncology Group. Invest New Drugs. 2004 Aug;22(3):343-9. PubMed PMID: 15122083.

43: Van Laar ES, Roth S, Weitman S, MacDonald JR, Waters SJ. Activity of irofulven against human pancreatic carcinoma cell lines in vitro and in vivo. Anticancer Res. 2004 Jan-Feb;24(1):59-65. PubMed PMID: 15015576.

44: Van Laar ES, Weitman S, MacDonald JR, Waters SJ. Antitumor activity of irofulven monotherapy and in combination with mitoxantrone or docetaxel against human prostate cancer models. Prostate. 2004 Apr 1;59(1):22-32. PubMed PMID: 14991863.

45: Dick RA, Yu X, Kensler TW. NADPH alkenal/one oxidoreductase activity determines sensitivity of cancer cells to the chemotherapeutic alkylating agent irofulven. Clin Cancer Res. 2004 Feb 15;10(4):1492-9. PubMed PMID: 14977853.

46: McMorris TC, Staake MD, Kelner MJ. Synthesis and biological activity of enantiomers of antitumor irofulven. J Org Chem. 2004 Feb 6;69(3):619-23. PubMed PMID: 14750783.

47: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Nov;25(9):747-71. PubMed PMID: 14685303.

48: Kulke MH. Advanced pancreatic cancer: is there a role for combination therapy? Expert Rev Anticancer Ther. 2003 Oct;3(5):729-39. Review. PubMed PMID: 14599095.

49: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Sep;25(7):565-97. PubMed PMID: 14571286.

50: Poindessous V, Koeppel F, Raymond E, Cvitkovic E, Waters SJ, Larsen AK. Enhanced antitumor activity of irofulven in combination with 5-fluorouracil and cisplatin in human colon and ovarian carcinoma cells. Int J Oncol. 2003 Nov;23(5):1347-55. PubMed PMID: 14532976.

51: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Jul-Aug;25(6):483-506. PubMed PMID: 12949633.

52: Poindessous V, Koeppel F, Raymond E, Comisso M, Waters SJ, Larsen AK. Marked activity of irofulven toward human carcinoma cells: comparison with cisplatin and ecteinascidin. Clin Cancer Res. 2003 Jul;9(7):2817-25. PubMed PMID: 12855662.

53: Urien S, Alexandre J, Raymond E, Brain E, Smith S, Shah A, Cvitkovic E, Lokiec F. Phase I population pharmacokinetics of irofulven. Anticancer Drugs. 2003 Jun;14(5):353-8. PubMed PMID: 12782941.

54: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. March 2003. Methods Find Exp Clin Pharmacol. 2003 Mar;25(2):145-68. PubMed PMID: 12731460.

55: Nasta SD, Hoff PM, George CS, Neubauer M, Cohen SC, Abbruzzese J, Winn R, Pazdur RM. Phase II study of MGI-114 administered intravenously for 5 days every 28 days to patients with metastatic colorectal cancer. Am J Clin Oncol. 2003 Apr;26(2):132-4. PubMed PMID: 12714882.

56: Lansiaux A, Bailly C. [Perspectives on the oncologist pharmacopoeia]. Bull Cancer. 2003 Jan;90(1):25-30. French. PubMed PMID: 12609801.

57: McMorris TC, Moon SS, Kelner MJ. Reaction of irofulven with zinc and acid. J Nat Prod. 2003 Feb;66(2):310-2. PubMed PMID: 12608875.

58: Herzig MC, Trevino AV, Liang H, Salinas R, Waters SJ, MacDonald JR, Woynarowska BA, Woynarowski JM. Apoptosis induction by the dual-action DNA- and protein-reactive antitumor drug irofulven is largely Bcl-2-independent. Biochem Pharmacol. 2003 Feb 15;65(4):503-13. PubMed PMID: 12566077.

59: Jaspers NG, Raams A, Kelner MJ, Ng JM, Yamashita YM, Takeda S, McMorris TC, Hoeijmakers JH. Anti-tumour compounds illudin S and Irofulven induce DNA lesions ignored by global repair and exclusively processed by transcription- and replication-coupled repair pathways. DNA Repair (Amst). 2002 Dec 5;1(12):1027-38. PubMed PMID: 12531012.

60: Amato RJ, Perez C, Pagliaro L. Irofulven, a novel inhibitor of DNA synthesis, in metastatic renal cell cancer. Invest New Drugs. 2002 Nov;20(4):413-7. PubMed PMID: 12448659.

61: Baekelandt M. Irofulven (MGI Pharma). Curr Opin Investig Drugs. 2002 Oct;3(10):1517-26. Review. PubMed PMID: 12431030.

62: Leggas M, Stewart CF, Woo MH, Fouladi M, Cheshire PJ, Peterson JK, Friedman HS, Billups C, Houghton PJ. Relation between Irofulven (MGI-114) systemic exposure and tumor response in human solid tumor xenografts. Clin Cancer Res. 2002 Sep;8(9):3000-7. PubMed PMID: 12231547.

63: Pierson AS, Gibbs P, Richards J, Russ P, Eckhardt SG, Gonzalez R. A phase II study of Irofulven (MGI 114) in patients with stage IV melanoma. Invest New Drugs. 2002 Aug;20(3):357-62. PubMed PMID: 12201500.

64: Kelner MJ, McMorris TC, Rojas RJ, Trani NA, Velasco TR, Estes LA, Suthipinijtham P. Enhanced antitumor activity of irofulven in combination with antimitotic agents. Invest New Drugs. 2002 Aug;20(3):271-9. PubMed PMID: 12201490.

65: Anthoney DA, Twelves CJ. DNA: still a target worth aiming at? A review of new DNA-interactive agents. Am J Pharmacogenomics. 2001;1(1):67-81. Review. PubMed PMID: 12173316.

66: Woynarowska BA, Woynarowski JM. Preferential targeting of apoptosis in tumor versus normal cells. Biochim Biophys Acta. 2002 Jul 18;1587(2-3):309-17. Review. PubMed PMID: 12084473.

67: Wang W, Waters SJ, MacDonald JR, Roth C, Shentu S, Freeman J, Von Hoff DD, Miller AR. Irofulven (6-hydroxymethylacylfulvene, MGI 114)-induced apoptosis in human pancreatic cancer cells is mediated by ERK and JNK kinases. Anticancer Res. 2002 Mar-Apr;22(2A):559-64. PubMed PMID: 12014623.

68: Kelner MJ, McMorris TC, Rojas RJ, Trani NA, Estes L. Enhanced antitumor activity of irofulven in combination with thiotepa or mitomycin C. Cancer Chemother Pharmacol. 2002 May;49(5):412-8. Epub 2002 Feb 12. PubMed PMID: 11976836.

69: Herzig MC, Liang H, Johnson AE, Woynarowska B, Woynarowski JM. Irofulven induces apoptosis in breast cancer cells regardless of caspase-3 status. Breast Cancer Res Treat. 2002 Jan;71(2):133-43. PubMed PMID: 11883439.

70: Thomas JP, Arzoomanian R, Alberti D, Feierabend C, Binger K, Tutsch KD, Steele T, Marnocha R, Smith C, Smith S, MacDonald J, Wilding G, Bailey H. Phase I clinical and pharmacokinetic trial of irofulven. Cancer Chemother Pharmacol. 2001 Dec;48(6):467-72. PubMed PMID: 11800027.

71: Friedman HS, Keir ST, Houghton PJ, Lawless AA, Bigner DD, Waters SJ. Activity of irofulven (6-hydroxymethylacylfulvene) in the treatment of glioblastoma multiforme-derived xenografts in athymic mice. Cancer Chemother Pharmacol. 2001 Nov;48(5):413-6. PubMed PMID: 11761460.

72: Berg WJ, Schwartz L, Yu R, Mazumdar M, Motzer RJ. Phase II trial of irofulven (6-hydroxymethylacylfulvene) for patients with advanced renal cell carcinoma. Invest New Drugs. 2001;19(4):317-20. PubMed PMID: 11561691.

73: Woynarowska BAHigdon AL, Muñoz RM, Bushong P, Waters SJ. Changes in prostate-specific antigen (PSA) level correlate with growth inhibition of prostate cancer cells treated in vitro with a novel anticancer drug, irofulven. Invest New Drugs. 2001;19(4):283-91. PubMed PMID: 11561687.

74: McMorris TC, Yu J, Lira R, Dawe R, MacDonald JR, Waters SJ, Estes LA, Kelner MJ. Structure-activity studies of antitumor agent irofulven (hydroxymethylacylfulvene) and analogues. J Org Chem. 2001 Sep 7;66(18):6158-63. PubMed PMID: 11529745.

75: Wang W, Waters SJ, MacDonald JR, Von Hoff DD, Strodel WE, Miller AR. Irofulven (6-hydroxymethylacylfulvene, MGI 114) induces caspase 8 and 9-mediated apoptosis in human pancreatic adenocarcinoma cells. Anticancer Res. 2001 May-Jun;21(3B):1789-94. PubMed PMID: 11497260.

76: Sato Y, Kashimoto S, MacDonald JR, Nakano K. In vivo antitumour efficacy of MGI-114 (6-hydroxymethylacylfulvene, HMAF) in various human tumour xenograft models including several lung and gastric tumours. Eur J Cancer. 2001 Jul;37(11):1419-28. PubMed PMID: 11435075.

77: Dowell JE, Johnson DH, Rogers JS, Shyr Y, McCullough N, Krozely P, DeVore RF. A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with advanced non-small cell cancer previously treated with chemotherapy. Invest New Drugs. 2001;19(1):85-8. PubMed PMID: 11291837.

78: Giles F, Cortes J, Garcia-Manero G, Kornblau S, Estey E, Kwari M, Murgo A, Kantarjian H. Phase I study of irofulven (MGI 114), an acylfulvene illudin analog, in patients with acute leukemia. Invest New Drugs. 2001;19(1):13-20. PubMed PMID: 11291829.

79: Eckhardt SG, Baker SD, Britten CD, Hidalgo M, Siu L, Hammond LA, Villalona-Calero MA, Felton S, Drengler R, Kuhn JG, Clark GM, Smith SL, MacDonald JR, Smith C, Moczygemba J, Weitman S, Von Hoff DD, Rowinsky EK. Phase I and pharmacokinetic study of irofulven, a novel mushroom-derived cytotoxin, administered for five consecutive days every four weeks in patients with advanced solid malignancies. J Clin Oncol. 2000 Dec 15;18(24):4086-97. PubMed PMID: 11118470.

80: Hammond LA, Hilsenbeck SG, Eckhardt SG, Marty J, Mangold G, MacDonald JR, Rowinsky EK, Von Hoff DD, Weitman S. Enhanced antitumour activity of 6-hydroxymethylacylfulvene in combination with topotecan or paclitaxel in the MV522 lung carcinoma xenograft model. Eur J Cancer. 2000 Dec;36(18):2430-6. PubMed PMID: 11094320.

81: Woynarowska BA, Roberts K, Woynarowski JM, MacDonald JR, Herman TS. Targeting apoptosis by hydroxymethylacylfulvene in combination with gamma radiation in prostate tumor cells. Radiat Res. 2000 Oct;154(4):429-38. PubMed PMID: 11023607.

82: McMorris TC, Yu J, Ngo HT, Wang H, Kelner MJ. Preparation and biological activity of amino acid and peptide conjugates of antitumor hydroxymethylacylfulvene. J Med Chem. 2000 Sep 21;43(19):3577-80. PubMed PMID: 11000013.

83: Weitman S, Barrera H, Moore R, Gonzalez C, Marty J, Hilsenbeck S, MacDonald JR, Waters SJ, Von Hoff D. MGI 114: augmentation of antitumor activity when combined with topotecan. J Pediatr Hematol Oncol. 2000 Jul-Aug;22(4):306-14. PubMed PMID: 10959900.

84: Kelner MJ, McMorris TC, Estes LA, Oval MY, Rojas RJ, Lynn JR, Lanham KA, Samson KM. Efficacy of MGI 114 (HMAF) against the MRP+ metastatic MV522 lung carcinoma xenograft. Anticancer Drugs. 2000 Mar;11(3):217-24. PubMed PMID: 10831281.

85: Marshall RF, Arthaud LE, MacDonald JR. Evaluation of antidotes for extravasation injury produced by 6-hydroxymethylacylfulvene (MGI 114), a novel cytotoxic antitumor agent, in an intradermal toxicity model in rats. Cancer Chemother Pharmacol. 2000;45(5):397-401. PubMed PMID: 10803923.

86: Woynarowska BA, Woynarowski JM, Herzig MC, Roberts K, Higdon AL, MacDonald JR. Differential cytotoxicity and induction of apoptosis in tumor and normal cells by hydroxymethylacylfulvene (HMAF). Biochem Pharmacol. 2000 May 15;59(10):1217-26. PubMed PMID: 10736422.

87: Kelner MJ, McMorris TC, Estes L, Samson KM, Trani NA, MacDonald JR. Anti-leukemic action of the novel agent MGI 114 (HMAF) and synergistic action with topotecan. Leukemia. 2000 Jan;14(1):136-41. PubMed PMID: 10637489.

88: Hidalgo M, Izbicka E, Eckhardt SG, MacDonald JR, Cerna C, Gomez L, Rowinsky EK, Weitman SD, Von Hoff DD. Antitumor activity of MGI 114 (6-hydroxymethylacylfulvene, HMAF), a semisynthetic derivative of illudin S, against adult and pediatric human tumor colony-forming units. Anticancer Drugs. 1999 Oct;10(9):837-44. PubMed PMID: 10587294.

89: McMorris TC, Elayadi AN, Yu J, Hu Y, Kelner MJ. Metabolism of antitumor hydroxymethylacylfulvene by rat liver cytosol. Drug Metab Dispos. 1999 Sep;27(9):983-5. PubMed PMID: 10460795.

90: Kelner MJ, McMorris TC, Montoya MA, Estes L, Uglik SF, Rutherford M, Samson KM, Bagnell RD, Taetle R. Characterization of MGI 114 (HMAF) histiospecific toxicity in human tumor cell lines. Cancer Chemother Pharmacol. 1999;44(3):235-40. PubMed PMID: 10453725.

91: Herzig MC, Arnett B, MacDonald JR, Woynarowski JM. Drug uptake and cellular targets of hydroxymethylacylfulvene (HMAF). Biochem Pharmacol. 1999 Jul 15;58(2):217-25. PubMed PMID: 10423161.

92: McMorris TC. Discovery and development of sesquiterpenoid derived hydroxymethylacylfulvene: a new anticancer drug. Bioorg Med Chem. 1999 May;7(5):881-6. Review. PubMed PMID: 10400341.

93: Izbicka E, Davidson K, Lawrence R, Cote R, MacDonald JR, Von Hoff DD. Cytotoxic effects of MGI 114 are independent of tumor p53 or p21 expression. Anticancer Res. 1999 Mar-Apr;19(2A):1299-307. PubMed PMID: 10368691.

94: Murgo A, Cannon DJ, Blatner G, Cheson BD. Clinical trials referral resource. Clinical trials of MGI-114. Oncology (Williston Park). 1999 Feb;13(2):233, 237-8. PubMed PMID: 10079472.

95: Britten CD, Hilsenbeck SG, Eckhardt SG, Marty J, Mangold G, MacDonald JR, Rowinsky EK, Von Hoff DD, Weitman S. Enhanced antitumor activity of 6-hydroxymethylacylfulvene in combination with irinotecan and 5-fluorouracil in the HT29 human colon tumor xenograft model. Cancer Res. 1999 Mar 1;59(5):1049-53. PubMed PMID: 10070962.

96: Kelner MJ, McMorris TC, Estes L, Samson KM, Bagnell RD, Taetle R. Efficacy of MGI 114 (6-hydroxymethylacylfulvene, HMAF) against the mdr1/gp170 metastatic MV522 lung carcinoma xenograft. Eur J Cancer. 1998 May;34(6):908-13. PubMed PMID: 9797706.

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