IMEXON

Details

Stereochemistry	RACEMIC
Molecular Formula	C4H5N3O
Molecular Weight	111.102
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(=O)N2CC12

InChI

InChIKey=BIXBBIPTYBJTRY-UHFFFAOYSA-N

InChI=1S/C4H5N3O/c5-3-2-1-7(2)4(8)6-3/h2H,1H2,(H2,5,6,8)

HIDE SMILES / InChI

Molecular Formula	C4H5N3O
Molecular Weight	111.102
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.drugbank.ca/drugs/DB05003
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20571355 | https://www.ncbi.nlm.nih.gov/pubmed/25016003 | https://www.ncbi.nlm.nih.gov/pubmed/25078786 | https://www.ncbi.nlm.nih.gov/pubmed/22275514 | https://www.ncbi.nlm.nih.gov/pubmed/22998528

Imexon (INN, trade name Amplimexon) is a substance that is being studied in the treatment of some types of cancer, including pancreatic, lung, breast, prostate, melanoma, and multiple myeloma. Imexon is a thiol-binding small molecule which induces mitochondrial oxidation, a loss of membrane potential and cytochrome C, leading to apoptosis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
response to oxidative stress 20 Target ID: GO:0006979 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25078786	Activator 1430

Conditions

Condition	Modality	Highest Phase	Product
B-cell non-Hodgkin lymphoma 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25016003	Primary	Phase II 1132	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20571355	Primary	Phase II 1132	Unknown Approved Use Unknown
Malignant melanoma 22 Sources: https://clinicaltrials.gov/ct2/show/NCT00327600	Primary	Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
1700 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 1700 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1700 mg/m2, 1 times / day Co-administed with:: Docetaxel(Docetaxel was administered intravenously at a fixed dose of 75 mg/m(2) immediately following imexon on day 1 every 21 days.) Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636	DLT: Non-cardiac chest pain... Dose limiting toxicities: Non-cardiac chest pain (grade 3, 66.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636
1300 mg/m2 1 times / day multiple, intravenous MTD Dose: 1300 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1300 mg/m2, 1 times / day Co-administed with:: Docetaxel(Docetaxel was administered intravenously at a fixed dose of 75 mg/m(2) immediately following imexon on day 1 every 21 days.) Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636	Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636
875 mg/m2 1 times / day multiple, intravenous MTD Dose: 875 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 875 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782	unhealthy, ADULT n = 9 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782	Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 3, 11.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782
1000 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 1000 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1000 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782	DLT: Abdominal pain, Fatigue... Other AEs: Thrombocytopenia, Anemia... Dose limiting toxicities: Abdominal pain (grade 3, 50%) Fatigue (grade 3, 50%) Neutropenia (grade 4, 50%) Other AEs: Thrombocytopenia (grade 4, 50%) Anemia (grade 3, 50%) Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782
1500 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 1500 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1500 mg/m2, 1 times / day Co-administed with:: Docetaxel(Docetaxel was administered intravenously at a fixed dose of 75 mg/m(2) immediately following imexon on day 1 every 21 days.) Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636	unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636	DLT: Non-cardiac chest pain, Diarrhea... Dose limiting toxicities: Non-cardiac chest pain (grade 3, 40%) Diarrhea (grade 3, 40%) Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636

AEs

AE	Significance	Dose	Population
Non-cardiac chest pain	grade 3, 66.7% DLT	1700 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 1700 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1700 mg/m2, 1 times / day Co-administed with:: Docetaxel(Docetaxel was administered intravenously at a fixed dose of 75 mg/m(2) immediately following imexon on day 1 every 21 days.) Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636
Thrombocytopenia	grade 3, 11.1%	875 mg/m2 1 times / day multiple, intravenous MTD Dose: 875 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 875 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782	unhealthy, ADULT n = 9 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782
Anemia	grade 3, 50%	1000 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 1000 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1000 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782
Abdominal pain	grade 3, 50% DLT	1000 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 1000 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1000 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782
Fatigue	grade 3, 50% DLT	1000 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 1000 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1000 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782
Thrombocytopenia	grade 4, 50%	1000 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 1000 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1000 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782
Neutropenia	grade 4, 50% DLT	1000 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 1000 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1000 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/17470869 Page: p.1781, 1782
Diarrhea	grade 3, 40% DLT	1500 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 1500 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1500 mg/m2, 1 times / day Co-administed with:: Docetaxel(Docetaxel was administered intravenously at a fixed dose of 75 mg/m(2) immediately following imexon on day 1 every 21 days.) Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636	unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636
Non-cardiac chest pain	grade 3, 40% DLT	1500 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 1500 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1500 mg/m2, 1 times / day Co-administed with:: Docetaxel(Docetaxel was administered intravenously at a fixed dose of 75 mg/m(2) immediately following imexon on day 1 every 21 days.) Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636	unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/19499186 Page: p.636

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-044023	http://www.3bsc.com/index/pro_info.php?id=76215
AA Blocks	AA00EIOJ	https://www.aablocks.com/goods/Goods/detail?id=AA00EIOJ
AHH Chemical co.,ltd	MT-42491	http://www.ahhchemical.com/product/MT-42491.html
Achemtek	0102-013901	http://www.achemtek.com/59643-91-3
Ambinter	Amb22295837	http://www.ambinter.com/reference/22295837
Ambinter	Amb22352757	http://www.ambinter.com/reference/22352757
ChemMol	49424589	http://www.chemmol.com/chemmol/49424589.html
ChemMol	99111522	http://www.chemmol.com/chemmol/99111522.html
DC Chemicals	DC20669	http://www.dcchemicals.com/product_show-DC20669.html
Lab Network	LN01345925	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01345925
MuseChem	I007277	https://www.musechem.com/product/I007277.html
OChem	19865	http://www.ocheminc.com/index.php?act=psearch&pid=643I913
Parchem	29138	http://www.parchem.com/chemical-supplier-distributor/Imexon-019138.aspx
eNovation Chemicals	D672873	https://www.enovationchem.com/ProductDetails.asp?ProductID=D672873
iChemical	EBD13413	http://www.ichemical.com/chemicals/cas-59643-91-3

PubMed

Title	Date	PubMed
Antiviral efficacy of Imexon in the Rauscher murine retrovirus AIDS model.	1990	1693633
Antiproliferative and antitumor activity of the 2-cyanoaziridine compound imexon on tumor cell lines and fresh tumor cells in vitro.	1992 Aug 19	1640482
Induction of oxidative stress and apoptosis in myeloma cells by the aziridine-containing agent imexon.	2000 Sep 15	10930529
Imexon-induced apoptosis in multiple myeloma tumor cells is caspase-8 dependent.	2004 Feb 15	14977852
Oxidative stress and apoptosis: a new treatment paradigm in cancer.	2006 Jan 1	16146732
The antitumor agent imexon activates antioxidant gene expression: evidence for an oxidative stress response.	2007 Jun 1	17545547
Redox-directed cancer therapeutics: molecular mechanisms and opportunities.	2009 Dec	19496700
Chemistry and pharmacology of imexon and related cyanoaziridines.	2012	22998528

Patents

Sample Use Guides

In Vivo Use Guide

Imexon was administered at 1000 mg/m2 IV over 60 minutes daily for the first 5 days of each 21-day treatment cycle. Treatment continued until disease progression or unacceptable toxicity

Route of Administration: Intravenous

In Vitro Use Guide

Colony-forming assays were conducted on MiaPaca-2 cells transfected with eIF2B5 or nontargeting siRNA (Dharmacon ON-TARGET plus SmartPool siRNA), followed by exposure to imexon for an additional 72 hours. Imexon was removed and cells were then plated in MethoCult (StemCell Technologies, Inc.) following the manufacturer's instructions and incubated for 7 to 10 days, and colony formation (>50 cells) was monitored by manual colony counting using a scoring grid.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:33:12 GMT 2023` Edited by `admin` on `Fri Dec 15 16:33:12 GMT 2023`
Record UNII	8F63U28T2V
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

IMEXON

Official Name

English

NSC-313425

Code

English

IMEXON [USAN]

Common Name

English

imexon [INN]

Common Name

English

Imexon [WHO-DD]

Common Name

English

IMEXON [MART.]

Common Name

English

(5RS)-4-Amino-1,3-diazabicyclo[3.1.0]hex-3-en-2-one

Systematic Name

English

1,3-DIAZABICYCLO(3.1.0)HEX-3-EN-2-ONE, 4-AMINO-

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

142501