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Details

Stereochemistry ACHIRAL
Molecular Formula C6H14ClN3O5S2
Molecular Weight 307.775
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LAROMUSTINE

SMILES

CNC(=O)N(N(CCCl)S(C)(=O)=O)S(C)(=O)=O

InChI

InChIKey=PVCULFYROUOVGJ-UHFFFAOYSA-N
InChI=1S/C6H14ClN3O5S2/c1-8-6(11)10(17(3,14)15)9(5-4-7)16(2,12)13/h4-5H2,1-3H3,(H,8,11)

HIDE SMILES / InChI
Molecular Formula C6H14ClN3O5S2
Molecular Weight 307.775
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

LAROMUSTINE is a sulfonylhydrazine alkylating agent. It is metabolized to yield a chloroethylating compound (VNP-4090-CE) and a carbamoylating compound (methyl isocyanate). The former is primarily responsible for the antineoplastic effect of LAROMUSTINE. It alkylates the O6 position of guanine, resulting in DNA crosslinking, strand breaks, chromosomal aberrations, and disruption of DNA synthesis. The carbamoylating species contribute to antitumor activity by inhibiting O6-alkylguanine transferase, an enzyme involved with DNA repair. It was studied in the treatment of several types of cancer, however, its development was discontinued.

Originator

Approval Year

Unknown
149124
PubMed

PubMed

TitleDatePubMed
Influence of glutathione and glutathione S-transferases on DNA interstrand cross-link formation by 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine, the active anticancer moiety generated by laromustine.
2014-08-18
Quantitative relationship between guanine O(6)-alkyl lesions produced by Onrigin™ and tumor resistance by O(6)-alkylguanine-DNA alkyltransferase.
2010-11-01
Reductive activation of the prodrug 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119) selectively occurs in oxygen-deficient cells and overcomes O(6)-alkylguanine-DNA alkyltransferase mediated KS119 tumor cell resistance.
2010-06-01
Gateways to clinical trials.
2010-06
Phase I study of temozolomide and laromustine (VNP40101M) in patients with relapsed or refractory leukemia.
2010-06
Novel therapies for myelodysplastic syndromes.
2010-04
Laromustine (cloretazine).
2010-03
Single-agent laromustine, a novel alkylating agent, has significant activity in older patients with previously untreated poor-risk acute myeloid leukemia.
2010-02-10
Toxicity of laromustine plus high-dose cytarabine in patients with relapsed acute myeloid leukemia.
2010-01-14
Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse.
2009-11-05
Clinical activity of laromustine (Onrigin™) in hematologic malignancies.
2009-10
An in vitro evaluation of the victim and perpetrator potential of the anticancer agent laromustine (VNP40101M), based on reaction phenotyping and inhibition and induction of cytochrome P450 enzymes.
2009-09
Laromustine: the return of alkylators to non-myeloablative therapy of AML.
2009-08
Effect of cloretazine (VNP40101M) on acute myeloid leukaemia blast cells in vitro as a single agent and combined with cytarabine and daunorubicin.
2009-08
Gateways to clinical trials.
2009-05
Gateways to clinical trials.
2009-04
Inhibition of human DNA polymerase beta activity by the anticancer prodrug Cloretazine.
2009-01-16
Laromustine, a sulfonyl hydrolyzing alkylating prodrug for cancer therapy.
2009-01
New agents for the treatment of AML recent study findings.
2008-11
Lethality to leukemia cell lines of DNA interstrand cross-links generated by Cloretazine derived alkylating species.
2008-10
Initial testing of VNP40101M (Cloretazine) by the pediatric preclinical testing program.
2008-09
Acute myeloid leukemia in the elderly: conventional and novel treatment approaches.
2008-07
Gateways to clinical trials.
2008-05
Phase I trial of VNP40101M (Cloretazine) in children with recurrent brain tumors: a pediatric brain tumor consortium study.
2008-02-15
Activity of VNP40101M (Cloretazine) in the treatment of CNS tumor xenografts in athymic mice.
2007-07
Determination of Cloretazine (VNP40101M) and its active metabolite (VNP4090CE) in human plasma by liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS).
2007-06-15
Bendamustine and cloretazine: alkylators with sharply contrasting activity in AML.
2007-06
Anti-tumor efficacy of Cloretazine (VNP40101M) alone and in combination with fludarabine in murine tumor and human xenograft tumor models.
2007-06
Nitric oxide donors attenuate clongenic potential in rat C6 glioma cells treated with alkylating chemotherapeutic agents.
2007-05-11
Advances in the management of AML in the elderly.
2007-03
American Society of Hematology--48th Annual Meeting and Exposition. Therapeutic approaches for hematological cancers. 9-12 December 2006 Orlando, FL, USA.
2007-02
Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia.
2007-01-01
Phase II study of Cloretazine for the treatment of adults with recurrent glioblastoma multiforme.
2007-01
A phase II study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients with very high risk relapsed acute myeloid leukemia.
2006-12
Mode of action of the chloroethylating and carbamoylating moieties of the prodrug cloretazine.
2006-04
Cloretazine for the treatment of acute myeloid leukemia.
2006-03
Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia.
2005-11-01
Role of O6-alkylguanine-DNA alkyltransferase in the cytotoxic activity of cloretazine.
2005-11
Differential inhibition of cellular glutathione reductase activity by isocyanates generated from the antitumor prodrugs Cloretazine and BCNU.
2005-05-15
A phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer.
2005-03
The antineoplastic efficacy of the prodrug Cloretazine is produced by the synergistic interaction of carbamoylating and alkylating products of its activation.
2005
A Phase I and pharmacokinetic study of VNP40101M, a novel sulfonylhydrazine alkylating agent, in patients with refractory leukemia.
2004-05-01
1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): I. Direct inhibition of O6-alkylguanine-DNA alkyltransferase (AGT) by electrophilic species generated by decomposition.
2004-04
1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): II. Role of O6-alkylguanine-DNA alkyltransferase in cytotoxicity.
2004-04
Toxicological evaluation of 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylaminocarbonyl)hydrazine (VNP40101M), a novel alkylating agent with potential antitumor activity, with intravenous administration in rats and dogs.
2002-04-09
Pharmacokinetics, mass balance, and tissue distribution of a novel DNA alkylating agent, VNP40101M, in rat.
2002
Pharmaceutical development and manufacturing of a parenteral formulation of a novel antitumor agent, VNP40101M.
2001-08-26
1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylamino)carbonylhydrazine (101M): a novel sulfonylhydrazine prodrug with broad-spectrum antineoplastic activity.
2001-04-01
Patents

Patents

05256820
2
05637619
2
08026395
3
20040121940
2
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:09:58 GMT 2025
Edited
by admin
on Mon Mar 31 18:09:58 GMT 2025
Record UNII
14J2G0U3NQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CLORETAZINE
Preferred Name English
LAROMUSTINE
DASH   INN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
ONRIGIN
Brand Name English
LAROMUSTINE [MART.]
Common Name English
NSC-734246
Code English
VNP40101M
Code English
laromustine [INN]
Common Name English
Laromustine [WHO-DD]
Common Name English
VNP-40101M
Code English
LAROMUSTIN
Common Name English
LAROMUSTINE [USAN]
Common Name English
LAROMUSTINE [MI]
Common Name English
2-(2-CHLOROETHYL)-N-METHYL-1,2-BIS(METHYLSULFONYL)HYDRAZINECARBOXAMIDE
Systematic Name English
1,2-BIS(METHYLSULFONYL)-1-(2-CHLOROETHYL)-2-((METHYLAMINO)CARBONYL)HYDRAZINE
Systematic Name English
101M
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 424014
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
FDA ORPHAN DRUG 194104
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
EU-Orphan Drug EU/3/05/332
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
NCI_THESAURUS C1590
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
NCI_THESAURUS C2134
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
Code System Code Type Description
INN
8936
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
CAS
173424-77-6
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
SMS_ID
100000124522
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
MESH
C483604
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
EVMPD
SUB32202
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
FDA UNII
14J2G0U3NQ
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
NCI_THESAURUS
C2653
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
MERCK INDEX
m6695
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY Merck Index
DRUG BANK
DB05817
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
PUBCHEM
3081349
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
USAN
SS-85
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
EPA CompTox
DTXSID30169614
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
NSC
734246
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
ChEMBL
CHEMBL167691
Created by admin on Mon Mar 31 18:09:58 GMT 2025 , Edited by admin on Mon Mar 31 18:09:58 GMT 2025
PRIMARY
Related Record Type Details
Structure of S-(N-METHYLCARBAMOYL)GLUTATHIONE
METABOLITE -> PARENT
Structure of S-(N-METHYLCARBAMOYL)-L-CYSTEINE
METABOLITE -> PARENT
Structure of N-ACETYL-S-(2-(METHYLSULFONYL)ETHYL)-L-CYSTEINE
METABOLITE -> PARENT
Structure of N-ACETYL-S-(2-(2-(METHYLSULFONYL)HYDRAZINYLIDENE)ETHYL)-L-CYSTEINE
METABOLITE -> PARENT
Structure of VNP-4090CE
METABOLITE ACTIVE -> PRODRUG
Structure of L-.GAMMA.-GLUTAMYL-S-(2-(2-(METHYLSULFONYL)HYDRAZINYLIDENE)ETHYL)-L-CYSTEINYL-GLYCINE
METABOLITE -> PARENT
Structure of S-(2-(METHYLSULFONYL)ETHYL)GLUTATHIONE
METABOLITE -> PARENT
IN-VITRO
Structure of S-(2-(METHYLSULFONYL)ETHYL)-L-CYSTEINE
METABOLITE -> PARENT
Structure of N-ACETYL-S-((METHYLAMINO)CARBONYL)-L-CYSTEINE
METABOLITE -> PARENT
Related Record Type Details
Structure of VNP-4090CE
ACTIVE MOIETY
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