Irofulven

Irofulven
Names
Preferred IUPAC name
(6′R)-6′-Hydroxy-3′-(hydroxymethyl)-2′,4′,6′-trimethylspiro[cyclopropane-1,5′-inden]-7′(6′H)-one
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
KEGG
UNII
  • InChI=1S/C15H18O3/c1-8-6-10-12(11(8)7-16)9(2)15(4-5-15)14(3,18)13(10)17/h6,16,18H,4-5,7H2,1-3H3/t14-/m0/s1 checkY
    Key: NICJCIQSJJKZAH-AWEZNQCLSA-N checkY
  • InChI=1/C15H18O3/c1-8-6-10-12(11(8)7-16)9(2)15(4-5-15)14(3,18)13(10)17/h6,16,18H,4-5,7H2,1-3H3/t14-/m0/s1
    Key: NICJCIQSJJKZAH-AWEZNQCLBL
  • O=C1C/3=C/C(=C(C\3=C(/C2([C@]1(O)C)CC2)C)CO)C
Properties
C15H18O3
Molar mass 246.302 g/mol
Density 1.285 g/mL
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Irofulven or 6-hydroxymethylacylfulvene (also known as HMAF of MGI-114) is an experimental antitumor agent.[1][2] It belongs to the family of drugs called alkylating agents.

It inhibits the DNA replication of cells deficient in nucleotide excision repair in culture.[3][4]

Irofulven is an analogue of illudin S, a sesquiterpene toxin found in the Jack 'o' Lantern mushroom (Omphalotus illudens). The compound was originally synthesized by Dr. Trevor McMorris and found to have anticancer properties in mice by Dr. Michael J Kelner.[5]

  1. ^ Escargueil, A. E.; Poindessous, V.; Soares, D. G.; Sarasin, A.; Cook, P. R.; Larsen, A. K. (April 2008). "Influence of Irofulven, a Transcription-Coupled Repair-Specific Antitumor Agent, on RNA Polymerase Activity, Stability and Dynamics in Living Mammalian Cells". Journal of Cell Science. 121 (Pt 8): 1275–1283. doi:10.1242/jcs.023259. PMID 18388315. S2CID 9282024.
  2. ^ Kelner, M. J.; McMorris, T. C.; Estes, L.; Wang, W.; Samson, K. M.; Taetle, R. (1996). "Efficacy of HMAF (MGI-114) in the MV522 Metastatic Lung Carcinoma Xenograft Model Nonresponsive to Traditional Anticancer Agents". Investigational New Drugs. 14 (2): 161–167. doi:10.1007/BF00210787. PMID 8913837. S2CID 8439510.
  3. ^ Wang, Y.; Wiltshire, T.; Senft, J.; Reed, E.; Wang, W. (February 2007). "Irofulven Induces Replication-Dependent CHK2 Activation Related to p53 Status". Biochemical Pharmacology. 73 (4): 469–480. doi:10.1016/j.bcp.2006.10.023. PMC 1800887. PMID 17118344.
  4. ^ Börcsök, Judit; Sztupinszki, Zsofia; Bekele, Raie; Gao, Sizhi P.; Diossy, Miklos; Samant, Amruta S.; Dillon, Kasia M.; Tisza, Viktoria; Spisák, Sándor; Rusz, Orsolya; Csabai, Istvan; Pappot, Helle; Frazier, Zoë J.; Konieczkowski, David J.; Liu, David (2021-04-01). "Identification of a Synthetic Lethal Relationship between Nucleotide Excision Repair Deficiency and Irofulven Sensitivity in Urothelial Cancer". Clinical Cancer Research. 27 (7): 2011–2022. doi:10.1158/1078-0432.CCR-20-3316. ISSN 1557-3265. PMC 8026514. PMID 33208343.
  5. ^ MacDonald, J. R.; Muscoplat, C. C.; Dexter, D. L.; Mangold, G. L.; Chen, S. F.; Kelner, M. J.; McMorris, T. C.; Von Hoff, D. D. (1997). "Preclinical Antitumor Activity of 6-hydroxymethylacylfulvene, a Semisynthetic Derivative of the Mushroom Toxin Illudin S" (PDF). Cancer Research. 57 (2): 279–283. PMID 9000568.