LAROMUSTINE

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/mesh/67483604 | https://www.ncbi.nlm.nih.gov/pubmed/19127504 | https://www.fdanews.com/articles/123139-vion-pharmaceuticals-files-bankruptcy-after-fda-rejects-drug

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

PubMed

Title	Date	PubMed
Pharmaceutical development and manufacturing of a parenteral formulation of a novel antitumor agent, VNP40101M.	2001 Aug 26	14727873
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 Jan-Feb	11936896
1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): II. Role of O6-alkylguanine-DNA alkyltransferase in cytotoxicity.	2004 Apr	14685775
A Phase I and pharmacokinetic study of VNP40101M, a novel sulfonylhydrazine alkylating agent, in patients with refractory leukemia.	2004 May 1	15131024
Differential inhibition of cellular glutathione reductase activity by isocyanates generated from the antitumor prodrugs Cloretazine and BCNU.	2005 May 15	15857610
Role of O6-alkylguanine-DNA alkyltransferase in the cytotoxic activity of cloretazine.	2005 Nov	16275997
Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia.	2005 Nov 1	16278404
American Society of Hematology--48th Annual Meeting and Exposition. Therapeutic approaches for hematological cancers. 9-12 December 2006 Orlando, FL, USA.	2007 Feb	17285454
Advances in the management of AML in the elderly.	2007 Mar	17519879
Acute myeloid leukemia in the elderly: conventional and novel treatment approaches.	2008 Jul	18433953
Gateways to clinical trials.	2008 May	18773127
New agents for the treatment of AML recent study findings.	2008 Nov	19205109
Initial testing of VNP40101M (Cloretazine) by the pediatric preclinical testing program.	2008 Sep	18493996
Laromustine, a sulfonyl hydrolyzing alkylating prodrug for cancer therapy.	2009 Jan	19127504
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 Nov 5	19710500
Clinical activity of laromustine (Onrigin™) in hematologic malignancies.	2009 Oct	21083013
Gateways to clinical trials.	2010 Jun	20664824
Phase I study of temozolomide and laromustine (VNP40101M) in patients with relapsed or refractory leukemia.	2010 Jun	20511167
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 Jun 1	20005211
Laromustine (cloretazine).	2010 Mar	20163276
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 Aug 18	25012050

Patents

Name

Type

Language

LAROMUSTINE

Official Name

English

CLORETAZINE

Brand 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