Identification
- Generic Name
- Irofulven
- DrugBank Accession Number
- DB05786
- Background
A novel anti-cancer compound synthesized by scientists at the University of California, San Diego more than a decade ago from toxins of the poisonous jack-o-lantern mushroom, has been granted “fast track” status by the U.S. Food and Drug Administration (FDA) after demonstrating promise against one of the most deadly cancers.
MGI-114 (Irofulven) is currently being developed by MGI PHARMA, Inc., an emerging oncology-focused pharmaceutical company based in Minneapolis. Phase III clinical trials involving the drug have been underway since early 2001 at sites in the U.S. and Europe.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Irofulven (DB05786)
- Weight
- Average: 246.3016
Monoisotopic: 246.125594442 - Chemical Formula
- C15H18O3
- Synonyms
- 6-hydroxymethylacylfulvene
- HMAF
- Irofulven
- External IDs
- MGI 114
- MGI-114
- NSC-683863
Pharmacology
- Indication
Investigated for use/treatment in brain cancer, breast cancer, endometrial cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, pediatric indications, prostate cancer, and sarcoma.
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Not Available
- 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.
Target Actions Organism UFar upstream element-binding protein 1 Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareArticaine The risk or severity of methemoglobinemia can be increased when Irofulven is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Irofulven is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Irofulven is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Irofulven is combined with Bupivacaine. Butacaine The risk or severity of methemoglobinemia can be increased when Irofulven is combined with Butacaine. Butamben The risk or severity of methemoglobinemia can be increased when Irofulven is combined with Butamben. Capsaicin The risk or severity of methemoglobinemia can be increased when Irofulven is combined with Capsaicin. Chloroprocaine The risk or severity of methemoglobinemia can be increased when Irofulven is combined with Chloroprocaine. Cinchocaine The risk or severity of methemoglobinemia can be increased when Irofulven is combined with Cinchocaine. Cocaine The risk or severity of methemoglobinemia can be increased when Irofulven is combined with Cocaine. 
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- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Irofulven
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as cyclohexenones. These are compounds containing a cylohexenone moiety, which is a six-membered aliphatic ring that carries a ketone and has one endocyclic double bond.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbonyl compounds
- Direct Parent
- Cyclohexenones
- Alternative Parents
- Acyloins / Tertiary alcohols / Primary alcohols / Organic oxides / Hydrocarbon derivatives
- Substituents
- Acyloin / Alcohol / Aliphatic homopolycyclic compound / Cyclohexenone / Hydrocarbon derivative / Organic oxide / Primary alcohol / Tertiary alcohol
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 6B799IH05A
- CAS number
- 158440-71-2
- InChI Key
- NICJCIQSJJKZAH-AWEZNQCLSA-N
- 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
- IUPAC Name
- (6'R)-6'-hydroxy-3'-(hydroxymethyl)-2',4',6'-trimethyl-6',7'-dihydrospiro[cyclopropane-1,5'-inden]-7'-one
- SMILES
- CC1=C(CO)C2=C(C)C3(CC3)[C@@](C)(O)C(=O)C2=C1
References
- General References
- Kelner MJ, McMorris TC, Estes L, Samson KM, Trani NA, MacDonald JR: Anti-leukemic action of the novel agent MGI 114 (HMAF) and synergistic action with topotecan. Leukemia. 2000 Jan;14(1):136-41. [Article]
- Leggas M, Stewart CF, Woo MH, Fouladi M, Cheshire PJ, Peterson JK, Friedman HS, Billups C, Houghton PJ: Relation between Irofulven (MGI-114) systemic exposure and tumor response in human solid tumor xenografts. Clin Cancer Res. 2002 Sep;8(9):3000-7. [Article]
- External Links
- PubChem Compound
- 148189
- PubChem Substance
- 175427030
- ChemSpider
- 130640
- BindingDB
- 50410835
- ChEBI
- 135002
- ChEMBL
- CHEMBL118218
- ZINC
- ZINC000003916310
- Wikipedia
- Irofulven
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Pancreatic Cancer 1 2 Active Not Recruiting Treatment Metastatic Castration Resistant Prostate Cancer Patients 1 2 Completed Treatment Breast Cancer 1 2 Completed Treatment Cervical Cancer 1 2 Completed Treatment Colorectal Cancer 1 2 Completed Treatment Endometrial Cancer 1 2 Completed Treatment Fallopian Tube Cancer / Ovarian Cancer / Primary Peritoneal Cancer 1 2 Completed Treatment Gastric Cancer 1 2 Completed Treatment Lung Cancer 1 2 Completed Treatment Melanoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.52 mg/mL ALOGPS logP 1.19 ALOGPS logP 0.67 Chemaxon logS -2.7 ALOGPS pKa (Strongest Acidic) 12.77 Chemaxon pKa (Strongest Basic) -1.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 57.53 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 70.91 m3·mol-1 Chemaxon Polarizability 27.33 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.8897 Caco-2 permeable + 0.6632 P-glycoprotein substrate Substrate 0.6081 P-glycoprotein inhibitor I Non-inhibitor 0.8341 P-glycoprotein inhibitor II Non-inhibitor 0.7901 Renal organic cation transporter Non-inhibitor 0.7904 CYP450 2C9 substrate Non-substrate 0.8237 CYP450 2D6 substrate Non-substrate 0.8562 CYP450 3A4 substrate Substrate 0.6744 CYP450 1A2 substrate Non-inhibitor 0.5914 CYP450 2C9 inhibitor Non-inhibitor 0.7017 CYP450 2D6 inhibitor Non-inhibitor 0.8684 CYP450 2C19 inhibitor Non-inhibitor 0.7898 CYP450 3A4 inhibitor Non-inhibitor 0.8441 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5946 Ames test AMES toxic 0.8571 Carcinogenicity Non-carcinogens 0.9225 Biodegradation Not ready biodegradable 0.9325 Rat acute toxicity 2.0258 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9857 hERG inhibition (predictor II) Non-inhibitor 0.8462
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Transcriptional activator activity, rna polymerase ii distal enhancer sequence-specific binding
- Specific Function
- Regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. May act both as activator and repressor of transcription.
- Gene Name
- FUBP1
- Uniprot ID
- Q96AE4
- Uniprot Name
- Far upstream element-binding protein 1
- Molecular Weight
- 67560.205 Da
Drug created at November 18, 2007 18:27 / Updated at January 14, 2023 19:02