Identification
- Generic Name
- Imexon
- DrugBank Accession Number
- DB05003
- Background
Imexon is currently being studied for the treatment of pancreatic, lung, breast, prostate, melanoma, and multiple myeloma cancers. It belongs to the family of drugs called cyanoaziridine derivatives. Also called Amplimexon. Imexon is a cyanoaziridine derivative. Imexon is a thiol-binding small molecule which induces mitochondrial oxidation, a loss of membrane potential and cytochrome C, leading to apoptosis.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Imexon (DB05003)
- Weight
- Average: 111.102
Monoisotopic: 111.043261797 - Chemical Formula
- C4H5N3O
- Synonyms
- Imexon
Pharmacology
- Indication
Investigated for use/treatment in melanoma, multiple myeloma, ovarian cancer, pancreatic cancer, and solid tumors.
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Not Available
- Mechanism of action
Imexon enters the cell and binds to glutathione and other sulfhydryl compounds, effectively preventing them from scavenging the toxic free radicals. So, particularly in the rapidly dividing cancer cell, free radical build-up in the presence of imexon leads to changes in mitochondrial membrane potential and ultimately to the mitochondria swelling and bursting. Mitochondrial proteins, in particular cytochrome c, are released into the cytoplasm and this activates caspase-mediated apoptosis resulting in cancer cell death. This sequence of events has been well characterized and published in several papers in leading cancer journals. Imexon is probably the only cancer drug under development at this time which exploits this mechanism of action. Imexon is an inhibitor of ribonucleotide reductase, a key enzyme in DNA synthesis that is also a target for gemcitabine. Imexon is also a cell cycle inhibitor and in the presence of the drug cells accumulate in S phase.
Target Actions Organism URibonucleoside-diphosphate reductase subunit M2 Not Available Humans URibonucleoside-diphosphate reductase large subunit 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.Not Available
- Food Interactions
- Not Available
Products
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- Amplimexon
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrimidones. These are compounds that contain a pyrimidine ring, which bears a ketone. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazines
- Sub Class
- Pyrimidines and pyrimidine derivatives
- Direct Parent
- Pyrimidones
- Alternative Parents
- Hydropyrimidines / Imidazolines / Organic carbonic acids and derivatives / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Carboxamidines / Aziridines / Azacyclic compounds / Organopnictogen compounds / Organic oxides show 2 more
- Substituents
- 1,2,5,6-tetrahydropyrimidine / 3-imidazoline / Aliphatic heteropolycyclic compound / Amidine / Azacycle / Aziridine / Carbonic acid derivative / Carbonyl group / Carboximidamide / Carboxylic acid amidine show 11 more
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 8F63U28T2V
- CAS number
- 59643-91-3
- InChI Key
- BIXBBIPTYBJTRY-UHFFFAOYSA-N
- InChI
- InChI=1S/C4H5N3O/c5-3-2-1-7(2)4(8)6-3/h2H,1H2,(H2,5,6,8)
- IUPAC Name
- 4-amino-1,3-diazabicyclo[3.1.0]hex-3-en-2-one
- SMILES
- NC1=NC(=O)N2CC12
References
- General References
- Evens AM, Prachand S, Shi B, Paniaqua M, Gordon LI, Gartenhaus RB: Imexon-induced apoptosis in multiple myeloma tumor cells is caspase-8 dependent. Clin Cancer Res. 2004 Feb 15;10(4):1481-91. [Article]
- External Links
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Burkitt Lymphoma / Diffuse Large B-Cell Lymphoma (DLBCL) / Follicular Lymphoma ( FL) / Mantle Cell Lymphoma (MCL) / Marginal Zone Lymphoma (MZL) / Small Lymphocytic Lymphoma / Waldenström's Macroglobulinemia (WM) 1 2 Completed Treatment Pancreatic Neoplasms 1 2 Withdrawn Treatment Non-Small Cell Lung Carcinoma 1 1 Completed Treatment Breast Cancer / Non-Small Cell Lung Cancer (NSCLC) / Prostate Cancer 1 1 Completed Treatment Metastatic Cancer 1 1 Completed Treatment Pancreatic Adenocarcinoma 1 1, 2 Completed Treatment Melanoma, Malignant 1 1, 2 Completed Treatment Multiple Myeloma (MM) 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 71.4 mg/mL ALOGPS logP -1.9 ALOGPS logP -1.6 Chemaxon logS -0.19 ALOGPS pKa (Strongest Acidic) 19.16 Chemaxon pKa (Strongest Basic) 2.53 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 58.46 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 25.7 m3·mol-1 Chemaxon Polarizability 9.98 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9671 Blood Brain Barrier + 0.9785 Caco-2 permeable - 0.5161 P-glycoprotein substrate Non-substrate 0.6978 P-glycoprotein inhibitor I Non-inhibitor 0.96 P-glycoprotein inhibitor II Non-inhibitor 0.9684 Renal organic cation transporter Non-inhibitor 0.6417 CYP450 2C9 substrate Non-substrate 0.8211 CYP450 2D6 substrate Non-substrate 0.7443 CYP450 3A4 substrate Non-substrate 0.6099 CYP450 1A2 substrate Non-inhibitor 0.6 CYP450 2C9 inhibitor Non-inhibitor 0.9118 CYP450 2D6 inhibitor Non-inhibitor 0.9337 CYP450 2C19 inhibitor Non-inhibitor 0.9197 CYP450 3A4 inhibitor Non-inhibitor 0.9912 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9955 Ames test AMES toxic 0.6533 Carcinogenicity Non-carcinogens 0.9361 Biodegradation Not ready biodegradable 0.9883 Rat acute toxicity 2.6171 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9712 hERG inhibition (predictor II) Non-inhibitor 0.9436
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key 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
- Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
- Specific Function
- Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling.
- Gene Name
- RRM2
- Uniprot ID
- P31350
- Uniprot Name
- Ribonucleoside-diphosphate reductase subunit M2
- Molecular Weight
- 44877.25 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
- Specific Function
- Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
- Gene Name
- RRM1
- Uniprot ID
- P23921
- Uniprot Name
- Ribonucleoside-diphosphate reductase large subunit
- Molecular Weight
- 90069.375 Da
Drug created at October 21, 2007 22:23 / Updated at January 14, 2023 19:02