Irofulven - CAS 158440-71-2 Catalog number: BADC-00330

Description

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.

Synonyms

(6'R)-6'-Hydroxy-3'-(hydroxymethyl)-2',4',6'-trimethylspiro[cyclopropane-1,5'-[5H]inden]-7'(6'H)-one; (-)-(Hydroxymethyl)acylfulvene; (-)-Irofulven; HMAF; MGI 114; NSC 683863; 6-Hydroxymethylacylfulvene; Hydroxymethylacylfulvene; (R)-6'-Hydroxy-3'-(hydroxymethyl)-2',4',6'-trimethylspiro(cyclopropane-1,5'-(5H)inden)-7'(6'H)-one

IUPAC Name

(5'R)-5'-hydroxy-1'-(hydroxymethyl)-2',5',7'-trimethylspiro[cyclopropane-1,6'-indene]-4'-one

Canonical SMILES

CC1=C(C2=C(C3(CC3)C(C(=O)C2=C1)(C)O)C)CO

InChI

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

InChIKey

NICJCIQSJJKZAH-AWEZNQCLSA-N

Density

1.3±0.1 g/cm3

Solubility

Soluble in Chloroform (Slightly), Ethyl Acetate (Slightly)

Melting Point

127-129°C

Mechanism Of Action

MGI-114(Irofulven) has unique mechanism of action as an anti-tumor agent is due to its ability to be rapidly absorbed by tumor cells. Once inside the cells, the compound binds to DNA and protein targets. This binding interferes with DNA replication and cell division of tumor cells, leading to tumor-specific apoptotic cell death, or "cell suicide." During this process, tumor cells tend to automatically shut themselves down when they sense their function is compromised.

In Vitro

Cell cycle studies show that irofulven increases the proportion of cells in the S phase. Cisplatin-irofulven and oxaliplatin-irofulven combinations block cells in G1/S and potently induce apoptosis.

In Vivo

Single agent irofulven displayed cytotoxic effects against human colon HT29 cells, human breast cancer cell lines including MCF7, SKBR3, and ZR-75-1, and human ovarian cancer cell lines CAOV3, OVCAR3, and IGROV1, with OVCAR3 being the most sensitive cancer cell line (IC50: 2.4 microM). In all tested cell lines the oxaliplatin-irofulven combination led to clear evidence of synergistic activity. In HT29 and HT29/IF2, the sequence oxaliplatin followed by irofulven appears to be the most effective whereas in MCF7 cells, irofulven given prior to or simultaneously with oxaliplatin is more effective than the other schedule. The combination displays additive activity toward CAOV3 ovarian cells when irofulven was administered prior to or simultaneously with oxaliplatin and partially synergistic when oxaliplatin was followed by irofulven. In most of the cell lines, the sequence oxaliplatin followed by irofulven appears to be the most effective as compared to other schedules. A combination of irofulven with cisplatin has the same efficacy as with oxaliplatin for the same cell lines.

Clinical Trial Information

Appearance

Orange Solid

Purity

≥95%

Shipping

Room temperature

Storage

Store at -20°C under inert atmosphere

Boiling Point

501.0±45.0°C at 760 mmHg

Current Developer

MGI PHARMA