Imexon

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
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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Contraindications & Blackbox Warnings
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Pharmacodynamics

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.

TargetActionsOrganism
URibonucleoside-diphosphate reductase subunit M2Not AvailableHumans
URibonucleoside-diphosphate reductase large subunitNot AvailableHumans
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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Toxicity

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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International/Other Brands
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
  1. 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]
PubChem Compound
68791
PubChem Substance
175426928
ChemSpider
62031
BindingDB
50073659
ChEMBL
CHEMBL146428
Wikipedia
Imexon

Clinical Trials

Clinical Trials

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
PropertyValueSource
Water Solubility71.4 mg/mLALOGPS
logP-1.9ALOGPS
logP-1.6Chemaxon
logS-0.19ALOGPS
pKa (Strongest Acidic)19.16Chemaxon
pKa (Strongest Basic)2.53Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area58.46 Å2Chemaxon
Rotatable Bond Count0Chemaxon
Refractivity25.7 m3·mol-1Chemaxon
Polarizability9.98 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9671
Blood Brain Barrier+0.9785
Caco-2 permeable-0.5161
P-glycoprotein substrateNon-substrate0.6978
P-glycoprotein inhibitor INon-inhibitor0.96
P-glycoprotein inhibitor IINon-inhibitor0.9684
Renal organic cation transporterNon-inhibitor0.6417
CYP450 2C9 substrateNon-substrate0.8211
CYP450 2D6 substrateNon-substrate0.7443
CYP450 3A4 substrateNon-substrate0.6099
CYP450 1A2 substrateNon-inhibitor0.6
CYP450 2C9 inhibitorNon-inhibitor0.9118
CYP450 2D6 inhibitorNon-inhibitor0.9337
CYP450 2C19 inhibitorNon-inhibitor0.9197
CYP450 3A4 inhibitorNon-inhibitor0.9912
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9955
Ames testAMES toxic0.6533
CarcinogenicityNon-carcinogens0.9361
BiodegradationNot ready biodegradable0.9883
Rat acute toxicity2.6171 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9712
hERG inhibition (predictor II)Non-inhibitor0.9436
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0900000000-da2c170524277a835878
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-02t9-9500000000-e0934886c9a471dd19e0
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03xu-9400000000-0d5a820d6dff71442689
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9100000000-83b89166bc10a900fd35
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-b948688b7bee48faabb5
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00kf-9000000000-68f6514dbb3beb373d81
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-122.1956
predicted
DeepCCS 1.0 (2019)
[M+H]+124.40738
predicted
DeepCCS 1.0 (2019)
[M+Na]+133.22029
predicted
DeepCCS 1.0 (2019)

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