Laromustine

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 201705

CAS#: 173424-77-6

Description: Laromustine is a sulfonyl hydrazine prodrug with antineoplastic activity. Laromustine releases the DNA chloroethylating agent 90CE after entering the blood stream; 90CE chloroethylates alkylates the 06 position of guanine, resulting in DNA crosslinking, strand breaks, chromosomal aberrations, and disruption of DNA synthesis. Intracellular metabolism of this agent also releases methyl isocyanate which inhibits 06-alkyl-guanine transferase, an enzyme involved with DNA repair.


Chemical Structure

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Laromustine
CAS# 173424-77-6

Theoretical Analysis

MedKoo Cat#: 201705
Name: Laromustine
CAS#: 173424-77-6
Chemical Formula: C6H14ClN3O5S2
Exact Mass: 307.00634
Molecular Weight: 307.77
Elemental Analysis: C, 23.41; H, 4.58; Cl, 11.52; N, 13.65; O, 25.99; S, 20.84

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Synonym: VNP40101M; VNP-40101M; VNP 40101M; NSC734246; NSC 734246; NSC-734246; Cloretazine; US brand names: Cloretazine; Onrigin.

IUPAC/Chemical Name: 2-(2-chloroethyl)-N-methyl-1,2-bis(methylsulfonyl)hydrazinecarboxamide

InChi Key: PVCULFYROUOVGJ-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: O=S(N(CCCl)N(C(NC)=O)S(=O)(C)=O)(C)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not soluble in water.

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 307.77 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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 1: Nassar AF, Wisnewski A, King I. Metabolic disposition of the anti-cancer agent [(14)C]laromustine in male rats. Xenobiotica. 2015 Aug;45(8):711-21. doi: 10.3109/00498254.2015.1016475. Epub 2015 Mar 23. PubMed PMID: 25798740.

2: Ji W, Yang M, Praggastis A, Li Y, Zhou HJ, He Y, Ghazvinian R, Cincotta DJ, Rice KP, Min W. Carbamoylating activity associated with the activation of the antitumor agent laromustine inhibits angiogenesis by inducing ASK1-dependent endothelial cell death. PLoS One. 2014 Jul 28;9(7):e103224. doi: 10.1371/journal.pone.0103224. eCollection 2014. PubMed PMID: 25068797; PubMed Central PMCID: PMC4113355.

3: Penketh PG, Patridge E, Shyam K, Baumann RP, Zhu R, Ishiguro K, Sartorelli AC. 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. Chem Res Toxicol. 2014 Aug 18;27(8):1440-9. doi: 10.1021/tx500197t. Epub 2014 Jul 17. PubMed PMID: 25012050; PubMed Central PMCID: PMC4137992.

4: Penketh PG, Shyam K, Zhu R, Baumann RP, Ishiguro K, Sartorelli AC. Influence of phosphate and phosphoesters on the decomposition pathway of 1,2-bis(methylsulfonyl)-1-(2-chloroethyhydrazine (90CE), the active anticancer moiety generated by Laromustine, KS119, and KS119W. Chem Res Toxicol. 2014 May 19;27(5):818-33. doi: 10.1021/tx500004y. Epub 2014 Mar 24. PubMed PMID: 24618018; PubMed Central PMCID: PMC4033638.

5: Rice KP, Klinkerch EJ, Gerber SA, Schleicher TR, Kraus TJ, Buros CM. Thioredoxin reductase is inhibited by the carbamoylating activity of the anticancer sulfonylhydrazine drug laromustine. Mol Cell Biochem. 2012 Nov;370(1-2):199-207. doi: 10.1007/s11010-012-1411-y. Epub 2012 Aug 5. PubMed PMID: 22864532; PubMed Central PMCID: PMC3469748.

6: Rockwell S, Liu Y, Seow HA, Ishiguro K, Baumann RP, Penketh PG, Shyam K, Akintujoye OM, Glazer PM, Sartorelli AC. Preclinical evaluation of Laromustine for use in combination with radiation therapy in the treatment of solid tumors. Int J Radiat Biol. 2012 Mar;88(3):277-85. doi: 10.3109/09553002.2012.638359. Epub 2011 Dec 20. PubMed PMID: 22111842; PubMed Central PMCID: PMC3660845.

7: Nassar AE, King I, Du J. Characterization of short-lived electrophilic metabolites of the anticancer agent laromustine (VNP40101M). Chem Res Toxicol. 2011 Apr 18;24(4):568-78. doi: 10.1021/tx100453t. Epub 2011 Mar 25. PubMed PMID: 21361357.

8: Alvarado Y, Swords R, Kelly KR, Giles FJ. Clinical activity of laromustine (Onrigin™) in hematologic malignancies. Expert Rev Hematol. 2009 Oct;2(5):481-8. doi: 10.1586/ehm.09.38. PubMed PMID: 21083013.

9: Rizzieri D, LoRusso S, Tse W, Khan K, Advani A, Moore J, Karsten V, Cahill A, Gerson SL. Phase I study of temozolomide and laromustine (VNP40101M) in patients with relapsed or refractory leukemia. Clin Lymphoma Myeloma Leuk. 2010 Jun;10(3):211-6. doi: 10.3816/CLML.2010.n.033. PubMed PMID: 20511167.

10: Vey N, Giles F. Laromustine (cloretazine). Expert Opin Pharmacother. 2010 Mar;11(4):657-67. doi: 10.1517/14656561003621232. Review. PubMed PMID: 20163276.

11: Deisseroth A, Farrell A, Justice R, Kane R, Sridhara R, Chen H, He K, Pazdur R. Toxicity of laromustine plus high-dose cytarabine in patients with relapsed acute myeloid leukemia. Blood. 2010 Jan 14;115(2):430. doi: 10.1182/blood-2009-09-244236. PubMed PMID: 20075171.

12: Schiller GJ, O'Brien SM, Pigneux A, Deangelo DJ, Vey N, Kell J, Solomon S, Stuart RK, Karsten V, Cahill AL, Albitar MX, Giles FJ. Single-agent laromustine, a novel alkylating agent, has significant activity in older patients with previously untreated poor-risk acute myeloid leukemia. J Clin Oncol. 2010 Feb 10;28(5):815-21. doi: 10.1200/JCO.2009.24.2008. Epub 2009 Dec 21. PubMed PMID: 20026800.

13: Giles F, Vey N, DeAngelo D, Seiter K, Stock W, Stuart R, Boskovic D, Pigneux A, Tallman M, Brandwein J, Kell J, Robak T, Staib P, Thomas X, Cahill A, Albitar M, O'Brien S. 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. Blood. 2009 Nov 5;114(19):4027-33. doi: 10.1182/blood-2009-06-229351. Epub 2009 Aug 26. PubMed PMID: 19710500.

14: Nassar AE, King I, Paris BL, Haupt L, Ndikum-Moffor F, Campbell R, Usuki E, Skibbe J, Brobst D, Ogilvie BW, Parkinson A. 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. Drug Metab Dispos. 2009 Sep;37(9):1922-30. doi: 10.1124/dmd.109.027516. Epub 2009 Jun 11. PubMed PMID: 19520774.

15: Giles FJ. Laromustine: the return of alkylators to non-myeloablative therapy of AML. Leuk Res. 2009 Aug;33(8):1022-3. doi: 10.1016/j.leukres.2009.02.002. Epub 2009 Mar 28. PubMed PMID: 19328547.

16: Pigneux A. Laromustine, a sulfonyl hydrolyzing alkylating prodrug for cancer therapy. IDrugs. 2009 Jan;12(1):39-53. Review. PubMed PMID: 19127504.



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