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MedKoo product information:
Laromustine
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MedKoo Code#: 201705
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Name:
Laromustine
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CAS#: 108736-35-2
Synonym:
VNP40101M；NSC734246。Cloretazine. US brand names: Cloretazine;
Onrigin. Code name: VNP40101M; Chemical structure names:
1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylaminocarbonyl)hydrazine;
2'-(2-chloroethyl)-N-methyl-1',2'-bis(methylsulfonyl)arbamohydrazide;
methanesulfonic acid, 1-(2-chloroethyl)-2-[(methylamino)carbonyl]-2-
(methylsulfonyl)hydrazide
IUPAC/Chemical name:
2-(2-chloroethyl)-N-methyl-1,2-bis(methylsulfonyl)hydrazinecarboxamide
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Chemical structure: |
Theoretical analysis
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Chemical Formula: C6H14ClN3O5S2
Exact Mass: 307.00634
Molecular Weight: 307.77
m/z: 307.00634 (100.0%), 309.00339 (32.0%),
309.00214 (9.0%), 308.00969 (6.5%), 310.99919 (2.9%), 310.00674
(2.1%), 308.00573 (1.6%), 308.00337 (1.1%), 309.01059 (1.0%)
Elemental Analysis: C, 23.41; H, 4.58; Cl,
11.52; N, 13.65; O, 25.99; S, 20.84
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Availability and price:
This agent is not in stock, which may be available through custom synthesis. To inquire quotation and lead time or to ask questions, please send email to
sales@medkoo.com to describe your needs. A representative
will respond your email shortly. We offer big discount for orders of bulk quantities.
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Quality control
data:
Product will be shipped with
supporting analytical data.
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Information about this agent
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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. Check for
active clinical trials or
closed clinical trials using this agent. (NCI
Thesaurus)
Current developer: Vion
Pharmaceuticals Inc。
1: 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 1;10(3):211-6.
PubMed PMID: 20511167.
2: Steensma DP. Novel therapies for myelodysplastic syndromes. Hematol
Oncol Clin North Am. 2010 Apr;24(2):423-41. PubMed PMID: 20359635.
3: Vey N, Giles F. Laromustine (cloretazine). Expert Opin Pharmacother.
2010 Mar;11(4):657-67. Review. PubMed PMID: 20163276.
4: 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.
PubMed PMID: 20075171.
5: 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. Epub 2009 Dec
21. PubMed PMID: 20026800.
6: 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. Epub 2009 Aug 26.
PubMed PMID: 19710500.
7: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp
Clin Pharmacol. 2009 May;31(4):263-98. PubMed PMID: 19557204.
8: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp
Clin Pharmacol. 2009 Apr;31(3):183-226. PubMed PMID: 19536362.
9: 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. Epub 2009 Jun 11. PubMed PMID: 19520774.
10: Giles FJ. Laromustine: the return of alkylators to non-myeloablative
therapy of AML. Leuk Res. 2009 Aug;33(8):1022-3. Epub 2009 Mar 28.
PubMed PMID: 19328547.
11: Morris KL, Adams JA, Liu Yin JA. Effect of cloretazine (VNP40101M)
on acute myeloid leukaemia blast cells in vitro as a single agent and
combined with cytarabine and daunorubicin. Leuk Res. 2009
Aug;33(8):1096-9. Epub 2009 Mar 5. PubMed PMID: 19268363.
12: Gore SD. New agents for the treatment of AML recent study findings.
Clin Adv Hematol Oncol. 2008 Nov;6(11):6-8. PubMed PMID: 19205109.
13: Pigneux A. Laromustine, a sulfonyl hydrolyzing alkylating prodrug
for cancer therapy. IDrugs. 2009 Jan;12(1):39-53. Review. PubMed PMID:
19127504.
14: Frederick AM, Davis ML, Rice KP. Inhibition of human DNA polymerase
beta activity by the anticancer prodrug Cloretazine. Biochem Biophys Res
Commun. 2009 Jan 16;378(3):419-23. Epub 2008 Nov 21. PubMed PMID:
19026985.
15: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp
Clin Pharmacol. 2008 May;30(4):313-31. PubMed PMID: 18773127.
16: Keir ST, Morton CL, Billups C, Smith MA, Houghton PJ, Gururangan S.
Initial testing of VNP40101M (Cloretazine) by the pediatric preclinical
testing program. Pediatr Blood Cancer. 2008 Sep;51(3):439-41. PubMed
PMID: 18493996; PubMed Central PMCID: PMC2836208.
17: Penketh PG, Baumann RP, Ishiguro K, Shyam K, Seow HA, Sartorelli AC.
Lethality to leukemia cell lines of DNA interstrand cross-links
generated by Cloretazine derived alkylating species. Leuk Res. 2008
Oct;32(10):1546-53. Epub 2008 May 13. PubMed PMID: 18479747.
18: Craig CM, Schiller GJ. Acute myeloid leukemia in the elderly:
conventional and novel treatment approaches. Blood Rev. 2008
Jul;22(4):221-34. Epub 2008 Apr 22. Review. PubMed PMID: 18433953.
19: Adams DJ, Sandvold ML, Myhren F, Jacobsen TF, Giles F, Rizzieri DA.
Anti proliferative activity of ELACY (CP-4055) in combination with
cloretazine (VNP40101M), idarubicin, gemcitabine, irinotecan and
topotecan in human leukemia and lymphoma cells. Leuk Lymphoma. 2008
Apr;49(4):786-97. PubMed PMID: 18398748; PubMed Central PMCID:
PMC2562023.
20: Gururangan S, Turner CD, Stewart CF, O'Shaughnessy M, Kocak M,
Poussaint TY, Phillips PC, Goldman S, Packer R, Pollack IF, Blaney SM,
Karsten V, Gerson SL, Boyett JM, Friedman HS, Kun LE. Phase I trial of
VNP40101M (Cloretazine) in children with recurrent brain tumors: a
pediatric brain tumor consortium study. Clin Cancer Res. 2008 Feb
15;14(4):1124-30. PubMed PMID: 18281546.
21: Giles FJ. Bendamustine and cloretazine: alkylators with sharply
contrasting activity in AML. Leuk Lymphoma. 2007 Jun;48(6):1064-6.
PubMed PMID: 17577766.
22: Badruddoja MA, Keir ST, King I, Zeidner J, Vredenburgh JJ, Muhlbaier
LH, Bigner DD, Friedman HS. Activity of VNP40101M (Cloretazine) in the
treatment of CNS tumor xenografts in athymic mice. Neuro Oncol. 2007
Jul;9(3):240-4. Epub 2007 May 23. PubMed PMID: 17522334; PubMed Central
PMCID: PMC1907418.
23: Estey EH. Advances in the management of AML in the elderly. Clin Adv
Hematol Oncol. 2007 Mar;5(3):185-7. PubMed PMID: 17519879.
24: Bai F, Minkin P, Fraga CH, O'Shaughnessy MA, Gururangan S, Stewart
CF. Determination of Cloretazine (VNP40101M) and its active metabolite
(VNP4090CE) in human plasma by liquid chromatography electrospray tandem
mass spectrometry (LC-ESI-MS/MS). J Chromatogr B Analyt Technol Biomed
Life Sci. 2007 Jun 15;853(1-2):97-104. Epub 2007 Mar 24. PubMed PMID:
17446145.
25: Tear S. American Society of Hematology--48th Annual Meeting and
Exposition. Therapeutic approaches for hematological cancers. 9-12
December 2006 Orlando, FL, USA. IDrugs. 2007 Feb;10(2):84-6. PubMed
PMID: 17285454.
26: Zheng LM, Li Z, Liu L, Song BL, King I. Anti-tumor efficacy of
Cloretazine (VNP40101M) alone and in combination with fludarabine in
murine tumor and human xenograft tumor models. Cancer Chemother
Pharmacol. 2007 Jun;60(1):45-51. Epub 2007 Jan 26. PubMed PMID:
17256135.
27: Giles F, Rizzieri D, Karp J, Vey N, Ravandi F, Faderl S, Khan KD,
Verhoef G, Wijermans P, Advani A, Roboz G, Kantarjian H, Bilgrami SF,
Ferrant A, Daenen SM, Karsten V, Cahill A, Albitar M, Mufti G, O'Brien
S. Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent,
in patients age 60 years or older with previously untreated acute
myeloid leukemia. J Clin Oncol. 2007 Jan 1;25(1):25-31. Epub 2006 Dec 4.
PubMed PMID: 17146105.
28: Badruddoja MA, Penne K, Desjardins A, Reardon DA, Rich JN, Quinn JA,
Sathornsumetee S, Friedman AH, Bigner DD, Herndon JE 2nd, Cahill A,
Friedman HS, Vredenburgh JJ. Phase II study of Cloretazine for the
treatment of adults with recurrent glioblastoma multiforme. Neuro Oncol.
2007 Jan;9(1):70-4. Epub 2006 Nov 15. PubMed PMID: 17108065; PubMed
Central PMCID: PMC1828104.
29: Ishiguro K, Seow HA, Penketh PG, Shyam K, Sartorelli AC. Mode of
action of the chloroethylating and carbamoylating moieties of the
prodrug cloretazine. Mol Cancer Ther. 2006 Apr;5(4):969-76. PubMed PMID:
16648568; PubMed Central PMCID: PMC2680221.
30: Giles F, Verstovsek S, Faderl S, Vey N, Karp J, Roboz G, Khan KD,
Cooper M, Bilgrami SF, Ferrant A, Daenen S, Karsten V, Cahill A, Albitar
M, Kantarjian H, O'Brien S, Feldman E. A phase II study of cloretazine
(VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients
with very high risk relapsed acute myeloid leukemia. Leuk Res. 2006
Dec;30(12):1591-5. Epub 2006 Mar 29. PubMed PMID: 16574225.
31: Vey N, Giles F. Cloretazine for the treatment of acute myeloid
leukemia. Expert Rev Anticancer Ther. 2006 Mar;6(3):321-8. Review.
PubMed PMID: 16503849.
32: Baumann RP, Seow HA, Shyam K, Penketh PG, Sartorelli AC. The
antineoplastic efficacy of the prodrug Cloretazine is produced by the
synergistic interaction of carbamoylating and alkylating products of its
activation. Oncol Res. 2005;15(6):313-25. PubMed PMID: 16408696.
33: Giles F, Verstovsek S, Thomas D, Gerson S, Cortes J, Faderl S,
Ferrajoli A, Ravandi F, Kornblau S, Garcia-Manero G, Jabbour E, O'Brien
S, Karsten V, Cahill A, Yee K, Albitar M, Sznol M, Kantarjian H. Phase I
study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating
agent, combined with cytarabine in patients with refractory leukemia.
Clin Cancer Res. 2005 Nov 1;11(21):7817-24. PubMed PMID: 16278404.
34: Ishiguro K, Shyam K, Penketh PG, Sartorelli AC. Role of
O6-alkylguanine-DNA alkyltransferase in the cytotoxic activity of
cloretazine. Mol Cancer Ther. 2005 Nov;4(11):1755-63. PubMed PMID:
16275997.
35: Seow HA, Penketh PG, Shyam K, Rockwell S, Sartorelli AC. 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hy
drazine: an anticancer agent targeting hypoxic cells. Proc Natl Acad Sci
U S A. 2005 Jun 28;102(26):9282-7. Epub 2005 Jun 17. PubMed PMID:
15964988; PubMed Central PMCID: PMC1166587.
36: Rice KP, Penketh PG, Shyam K, Sartorelli AC. Differential inhibition
of cellular glutathione reductase activity by isocyanates generated from
the antitumor prodrugs Cloretazine and BCNU. Biochem Pharmacol. 2005 May
15;69(10):1463-72. PubMed PMID: 15857610.
37: Murren J, Modiano M, Kummar S, Clairmont C, Egorin M, Chu E, Sznol
M. A phase I and pharmacokinetic study of VNP40101M, a new alkylating
agent, in patients with advanced or metastatic cancer. Invest New Drugs.
2005 Mar;23(2):123-35. PubMed PMID: 15744588.
38: Giles F, Thomas D, Garcia-Manero G, Faderl S, Cortes J, Verstovsek
S, Ferrajoli A, Jeha S, Beran M, Koller C, Andreeff M, Cahill A,
Clairmont C, Sznol M, Kantarjian H. A Phase I and pharmacokinetic study
of VNP40101M, a novel sulfonylhydrazine alkylating agent, in patients
with refractory leukemia. Clin Cancer Res. 2004 May 1;10(9):2908-17.
PubMed PMID: 15131024.
39: Krishna G, Hodnick WF, Lang W, Lin X, Karra S, Mao J, Almassian B.
Pharmaceutical development and manufacturing of a parenteral formulation
of a novel antitumor agent, VNP40101M. AAPS PharmSciTech. 2001 Aug
26;2(3):E14. PubMed PMID: 14727873.
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