Name: Irofulven
Brand: BOC Sciences
Price: 1565 USD
Availability: MadeToOrder

Size

Price

Stock

Quantity

5 mg

$1565

In stock

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

Appearance

Orange Solid

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

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.

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.

NCT Number	Condition Or Disease	Phase	Start Date	Sponsor	Status
NCT00033735	Pancreatic Cancer	Phase 3	2012-12-24	Eisai Inc.	Completed
NCT00005968	Melanoma (Skin)	Phase 2	2013-05-30	University of Colorado, Denver	Completed
NCT00374660	Liver Cancer	Phase 1	2015-07-01	Eisai Inc.	Unknown Verified June 2015 by Eisai Inc.. Recruitment status was Active, not recruiting
NCT00124527	Thyroid Cancer	Phase 2	2021-06-16	Eisai Inc.	Completed
NCT00003441	Colorectal Cancer	Phase 2	2018-10-25	M.D. Anderson Cancer Center	Completed

1. Natural sesquiterpenoids

Braulio M. Fraga. Nat. Prod. Rep., 2004, 21, 669–693

A formal synthesis of7-protoilludene has been described. The distribution of ptaquiloside has been studied in four Danish bracken populations in order to evaluate the transfer of this carcinogenic sesquiterpene from ferns to the soil. An approach to the synthesis of pteridanone, the aglycone of the glucoside pteridanoside, has been reported. Studies on the structure–activity relationship of illudin analogues possessing a spiro-cyclobutane ring have been carried out. Illudin S has been identified as the sole antiviral compound present in an extract of mature fruiting bodies ofOmphalotus illudens. A library of forty-nine illudinoids has been preparedvia a three-step synthesis and tested against three cancer cell lines. The reaction of the antitumour agent irofulven with zinc and acetic acid led to a series of compounds, which present a more reduced toxicity to human leukaemia than irofulven. Synthetic studies towards the framework construction of the fomannosane sesquiterpene illudosin have been reported.

2. Recent advances in the use of temporary silicon tethers in metal-mediated reactions

Sonia Bracegirdle and Edward A. Anderson*. Chem. Soc. Rev.,2010,39, 4114–4129

Finally, an equally impressive example of enyne RCM in total synthesis is illustrated by the Movassaghi group’s preparation of (-)-acylfulvene (51, Scheme 10) and (-)-irofulven, two members of the cytotoxic illudin family. Preparation of the disiloxane52was readily achievedviaunion of an appropriate alkyne and aldehyde, followed by silylation. This substrate is designed with great care, as TST ring-closing enyne metathesis must be achieved in the presence of an additional ‘spectator’ trisubstituted alkene, and for this the phenyl substituent proved crucial as a protecting group. Thus, initiation of the cascade cyclisation at the mono-substituted alkene was followed by dienyne RCM, terminating on the 1,1-disubstituted alkene, which afforded the 7,6-bicycle53in an outstanding 79% yield; notably, the use of less bulky or non-conjugated blocking groups on the trisubstituted alkene led to competing metathesis side-reactions.