IROFULVEN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H18O3
Molecular Weight	246.3016
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(CO)C2=C(C)C3(CC3)[C@@](C)(O)C(=O)C2=C1

InChI

InChIKey=NICJCIQSJJKZAH-AWEZNQCLSA-N

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

HIDE SMILES / InChI

Molecular Formula	C15H18O3
Molecular Weight	246.3016
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8864242 | https://www.cancer.gov/publications/dictionaries/cancer-drug/def/irofulven | https://oncologyventure.com/pipeline/2x-111-2/

IROFULVEN is a semisynthetic derivative of a natural sesquiterpene toxin illudin S, isolated from the fungus Omphalotus illudens. It alkylates DNA and protein macromolecules, forms adducts, and arrests cells in the S-phase of the cell cycle. It 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 P-glycoprotein than other alkylating agents. IROFULVEN has been evaluated in 19 clinical trials, predominantly in refractory prostate and ovarian cancer patients. Results were positive, including a 10% response rate in patients with prostate cancer previously treated with docetaxel and 13% in ovarian cancer patients relapsing between 6 and 12 months after standard treatment with carboplatin and paclitaxel.

Originator

Approval Year

PubMed

Title	Date	PubMed
Anti-leukemic action of the novel agent MGI 114 (HMAF) and synergistic action with topotecan.	2000 Jan	10637489
Phase I study of irofulven (MGI 114), an acylfulvene illudin analog, in patients with acute leukemia.	2001	11291829
In vivo antitumour efficacy of MGI-114 (6-hydroxymethylacylfulvene, HMAF) in various human tumour xenograft models including several lung and gastric tumours.	2001 Jul	11435075
Structure-activity studies of antitumor agent irofulven (hydroxymethylacylfulvene) and analogues.	2001 Sep 7	11529745
Irofulven induces apoptosis in breast cancer cells regardless of caspase-3 status.	2002 Jan	11883439
Enhanced antitumor activity of irofulven in combination with thiotepa or mitomycin C.	2002 May	11976836
Phase II study of MGI-114 administered intravenously for 5 days every 28 days to patients with metastatic colorectal cancer.	2003 Apr	12714882
Advanced pancreatic cancer: is there a role for combination therapy?	2003 Oct	14599095
Antitumor activity of irofulven monotherapy and in combination with mitoxantrone or docetaxel against human prostate cancer models.	2004 Apr 1	14991863
Irofulven cytotoxicity depends on transcription-coupled nucleotide excision repair and is correlated with XPG expression in solid tumor cells.	2004 Aug 15	15328203
Synthesis and biological activity of enantiomers of antitumor irofulven.	2004 Feb 6	14750783
Gateways to clinical trials.	2004 May	15319808
Phase I and pharmacokinetic study of irofulven administered weekly or biweekly in advanced solid tumor patients.	2004 May 15	15161692
Irofulven: resurgence for alkylating therapy in cancer?	2004 Nov	15640616
ATM-dependent CHK2 activation induced by anticancer agent, irofulven.	2004 Sep 17	15269203
Antitumor activity of irofulven against human ovarian cancer cell lines, human tumor colony-forming units, and xenografts.	2004 Sep-Oct	15361190
Cone damage in patients receiving high-dose irofulven treatment.	2005 Jan	15642808
Enhanced antitumor activity of irofulven in combination with irinotecan in pediatric solid tumor xenograft models.	2005 May	15503024
Phase I trial of irofulven (MGI 114) in pediatric patients with solid tumors.	2006 Aug	16317728
Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles.	2006 Oct	17020410
Comparison of antitumor activities in tumor xenograft treatment.	2007 Feb	16814615
Gateways to clinical trials.	2007 Jul-Aug	17922073
A phase I and pharmacokinetic study of irofulven and capecitabine administered every 2 weeks in patients with advanced solid tumors.	2007 Oct	17628744
Profiling patterns of glutathione reductase inhibition by the natural product illudin S and its acylfulvene analogues.	2009 Sep	19668867
A ubiquitin-binding domain in Cockayne syndrome B required for transcription-coupled nucleotide excision repair.	2010 Jun 11	20541997
Dissociation of CAK from core TFIIH reveals a functional link between XP-G/CS and the TFIIH disassembly state.	2010 Jun 8	20543986

Sample Use Guides

In Vivo Use Guide

The dose is 0.45 mg/kg, over a 30-minute infusion period by venous access at day 1 and 8 of a three-week cycle.

Route of Administration: Intravenous

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:57:48 UTC 2023` Edited by `admin` on `Fri Dec 15 15:57:48 UTC 2023`
Record UNII	6B799IH05A
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

IROFULVEN

Official Name

English

IROFULVEN [USAN]

Common Name

English

(R)-6'-HYDROXY-3'-(HYDROXYMETHYL)-2',4',6'-TRIMETHYLSPIRO(CYCLOPROPANE-1,5'-(5H)INDEN)-7'(6'H)-ONE

Systematic Name

English

MGI114

Code

English

Irofulven [WHO-DD]

Common Name

English

LP-100

Code

English

6-HYDROXYMETHYLACYLFULVENE

Common Name

English

irofulven [INN]

Common Name

English

HMAF

Common Name

English

NSC-683863

Code

English

(HYDROXYMETHYL)ACYLFULVENE

Common Name

English

IROFULVEN [MI]

Common Name

English

MGI-114

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

125399