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

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

Irofulven is a semisynthetic DNA-alkylating agent and a potent ADC cytotoxin used as an ADC payload in antibody-drug conjugates. Its cytotoxic mechanism involves alkylation of DNA, leading to DNA strand breaks, inhibition of replication, and induction of apoptosis in proliferating tumor cells. The molecular structure of Irofulven allows conjugation to antibodies via cleavable or non-cleavable linkers, facilitating targeted intracellular delivery in ADC applications.

Within antibody-drug conjugates, Irofulven is covalently attached to monoclonal antibodies using linkers that provide systemic stability and controlled payload release. The ADC remains inactive in circulation and is activated upon internalization into antigen-expressing tumor cells, where enzymatic cleavage releases Irofulven. This targeted delivery ensures cytotoxic activity is confined to tumor cells, minimizing off-target effects while maintaining precise antitumor mechanisms.

Applications of Irofulven include its use in ADCs targeting both solid tumors and hematologic malignancies. Its chemical compatibility with diverse linker chemistries allows optimization of conjugation efficiency, intracellular release kinetics, and pharmacokinetic behavior. Irofulven exhibits defined cytotoxicity in target-expressing cell lines and supports the development of ADCs with controlled DNA-damaging activity for tumor-targeted therapeutic applications.

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.

What is Irofulven?

Irofulven is a DNA-damaging cytotoxin derived from illudin S, used as an ADC payload. It forms covalent adducts with DNA, leading to strand breaks and apoptosis, making it suitable for targeted cancer therapy when conjugated to antibodies.

30/8/2017

We are interested in how Irofulven improves ADC efficacy.

Irofulven enhances ADC therapeutic performance by selectively inducing DNA damage in antigen-expressing cells. Conjugation to antibodies ensures precise delivery, reducing off-target effects and maximizing cytotoxic impact on tumor cells.

12/12/2017

Could you advise which linkers are suitable for Irofulven conjugation?

Irofulven is compatible with cleavable linkers such as peptide-based or disulfide linkers. These linkers enable controlled intracellular release, maintaining ADC stability in circulation while delivering the payload efficiently to target cells.

20/5/2020

Is Irofulven suitable for preclinical ADC studies?

Yes, Irofulven is widely used in preclinical ADC research to evaluate efficacy, cytotoxicity, and pharmacokinetics. It provides critical data for optimizing ADC design, linker selection, and therapeutic performance in early-stage studies.

4/12/2020

Dear team, what handling precautions are necessary for Irofulven?

Due to its potent DNA-damaging properties, Irofulven must be handled with strict safety protocols, including PPE, fume hoods, and controlled waste disposal to prevent accidental exposure during ADC development.

4/8/2022

— Dr. Jason Carter, Senior Scientist (USA)

Irofulven from BOC Sciences arrived with outstanding purity, enabling efficient ADC conjugation.

20/5/2020

— Dr. Richard Brown, Oncology Researcher (USA)

Irofulven from BOC Sciences arrived quickly and with full traceability, which is essential for regulated research projects.

4/8/2022

— Ms. Maria Schneider, Senior Scientist (Germany)

We were able to integrate Irofulven smoothly into our studies thanks to the compound’s high purity and proper documentation.

4/12/2020

— Dr. Andrew Clarke, Project Lead (UK)

The Irofulven compound performed as expected in conjugation studies, and the stability was impressive over extended storage.