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 |
|---|---|---|
| 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylamino)carbonylhydrazine (101M): a novel sulfonylhydrazine prodrug with broad-spectrum antineoplastic activity. | 2001 Apr 1 |
|
| Pharmaceutical development and manufacturing of a parenteral formulation of a novel antitumor agent, VNP40101M. | 2001 Aug 26 |
|
| Pharmacokinetics, mass balance, and tissue distribution of a novel DNA alkylating agent, VNP40101M, in rat. | 2002 |
|
| 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 |
|
| 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 Apr |
|
| 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): II. Role of O6-alkylguanine-DNA alkyltransferase in cytotoxicity. | 2004 Apr |
|
| A Phase I and pharmacokinetic study of VNP40101M, a novel sulfonylhydrazine alkylating agent, in patients with refractory leukemia. | 2004 May 1 |
|
| 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 new alkylating agent, in patients with advanced or metastatic cancer. | 2005 Mar |
|
| Differential inhibition of cellular glutathione reductase activity by isocyanates generated from the antitumor prodrugs Cloretazine and BCNU. | 2005 May 15 |
|
| Role of O6-alkylguanine-DNA alkyltransferase in the cytotoxic activity of cloretazine. | 2005 Nov |
|
| Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia. | 2005 Nov 1 |
|
| Mode of action of the chloroethylating and carbamoylating moieties of the prodrug cloretazine. | 2006 Apr |
|
| A phase II study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients with very high risk relapsed acute myeloid leukemia. | 2006 Dec |
|
| Cloretazine for the treatment of acute myeloid leukemia. | 2006 Mar |
|
| American Society of Hematology--48th Annual Meeting and Exposition. Therapeutic approaches for hematological cancers. 9-12 December 2006 Orlando, FL, USA. | 2007 Feb |
|
| Phase II study of Cloretazine for the treatment of adults with recurrent glioblastoma multiforme. | 2007 Jan |
|
| Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia. | 2007 Jan 1 |
|
| Activity of VNP40101M (Cloretazine) in the treatment of CNS tumor xenografts in athymic mice. | 2007 Jul |
|
| Bendamustine and cloretazine: alkylators with sharply contrasting activity in AML. | 2007 Jun |
|
| Anti-tumor efficacy of Cloretazine (VNP40101M) alone and in combination with fludarabine in murine tumor and human xenograft tumor models. | 2007 Jun |
|
| Determination of Cloretazine (VNP40101M) and its active metabolite (VNP4090CE) in human plasma by liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS). | 2007 Jun 15 |
|
| Advances in the management of AML in the elderly. | 2007 Mar |
|
| Nitric oxide donors attenuate clongenic potential in rat C6 glioma cells treated with alkylating chemotherapeutic agents. | 2007 May 11 |
|
| Phase I trial of VNP40101M (Cloretazine) in children with recurrent brain tumors: a pediatric brain tumor consortium study. | 2008 Feb 15 |
|
| Acute myeloid leukemia in the elderly: conventional and novel treatment approaches. | 2008 Jul |
|
| Gateways to clinical trials. | 2008 May |
|
| New agents for the treatment of AML recent study findings. | 2008 Nov |
|
| Lethality to leukemia cell lines of DNA interstrand cross-links generated by Cloretazine derived alkylating species. | 2008 Oct |
|
| Initial testing of VNP40101M (Cloretazine) by the pediatric preclinical testing program. | 2008 Sep |
|
| Gateways to clinical trials. | 2009 Apr |
|
| Laromustine: the return of alkylators to non-myeloablative therapy of AML. | 2009 Aug |
|
| Effect of cloretazine (VNP40101M) on acute myeloid leukaemia blast cells in vitro as a single agent and combined with cytarabine and daunorubicin. | 2009 Aug |
|
| Laromustine, a sulfonyl hydrolyzing alkylating prodrug for cancer therapy. | 2009 Jan |
|
| Inhibition of human DNA polymerase beta activity by the anticancer prodrug Cloretazine. | 2009 Jan 16 |
|
| Gateways to clinical trials. | 2009 May |
|
| 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 |
|
| Clinical activity of laromustine (Onrigin™) in hematologic malignancies. | 2009 Oct |
|
| 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 Sep |
|
| Novel therapies for myelodysplastic syndromes. | 2010 Apr |
|
| Single-agent laromustine, a novel alkylating agent, has significant activity in older patients with previously untreated poor-risk acute myeloid leukemia. | 2010 Feb 10 |
|
| Toxicity of laromustine plus high-dose cytarabine in patients with relapsed acute myeloid leukemia. | 2010 Jan 14 |
|
| Gateways to clinical trials. | 2010 Jun |
|
| Phase I study of temozolomide and laromustine (VNP40101M) in patients with relapsed or refractory leukemia. | 2010 Jun |
|
| 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 |
|
| Laromustine (cloretazine). | 2010 Mar |
|
| Quantitative relationship between guanine O(6)-alkyl lesions produced by Onrigin™ and tumor resistance by O(6)-alkylguanine-DNA alkyltransferase. | 2010 Nov 1 |
|
| 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 |
Patents
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 09:41:42 GMT 2023
by
admin
on
Sat Dec 16 09:41:42 GMT 2023
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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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