Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C4H11ClN2O4S2 |
| Molecular Weight | 250.724 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(=O)(=O)NN(CCCl)S(C)(=O)=O
InChI
InChIKey=QVKFHBWVOPWLGX-UHFFFAOYSA-N
InChI=1S/C4H11ClN2O4S2/c1-12(8,9)6-7(4-3-5)13(2,10)11/h6H,3-4H2,1-2H3
| Molecular Formula | C4H11ClN2O4S2 |
| Molecular Weight | 250.724 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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 |
|---|---|---|
| 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
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 22:47:44 GMT 2025
by
admin
on
Mon Mar 31 22:47:44 GMT 2025
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| Record UNII |
6ZE344986H
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| Record Status |
Validated (UNII)
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| Record Version |
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m6695
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127792-84-1
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