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 Mechlorethamine HCl

mechlorethamine hydrochloride is the hydrochloride salt of mechlorethamine, a nitrogen mustard and an analogue of sulfur mustard, with antineoplastic and immunosuppressive activities. Mechlorethamine is metabolized to an unstable, highly reactive ethyleniminium intemediate that alkylates DNA, particularly the 7 nitrogen of guanine residues, resulting in DNA base pair mismatching, DNA interstrand crosslinking, the inhibition of DNA repair and synthesis, cell-cycle arrest, and apoptosis. This agent also exhibits lympholytic properties. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

History

Successful clinical use of mechlorethamine gave birth to the field of anticancer chemotherapy. The drug is an analogue of mustard gas and was derived from chemical warfare research, in particular a 1943 accident in Bari, Italy which exposed civilians and soldiers-- it was noted that white cell counts of exposed patients decreased, suggesting a possible therapy for the cancer Hodgkin's lymphoma.

DRUG DESCRIPTION

MUSTARGEN, an antineoplastic nitrogen mustard also known as HN2 hydrochloride, is a nitrogen analog of sulfur mustard. It is a light yellow brown, crystalline, hygroscopic powder that is very soluble in water and also soluble in alcohol.
Mechlorethamine hydrochloride is designated chemically as 2-chloro-N-(2-chloroethyl)-N-methylethanamine hydrochloride. The molecular weight is 192.52 and the melting point is 108-111°C. The empirical formula is C5H11Cl2N•HCl, and the structural formula is: CH3N(CH2CH2Cl)2•HCl. Trituration of MUSTARGEN is a sterile, light yellow brown crystalline powder for injection by the intravenous or intracavitary routes after dissolution. Each vial of MUSTARGEN contains 10 mg of mechlorethamine hydrochloride triturated with sodium chloride q.s. 100 mg. When dissolved with 10 mL Sterile Water for Injection or 0.9% Sodium Chloride Injection, the resulting solution has a pH of 3-5 at a concentration of 1 mg mechlorethamine HCl per mL.

 1: Sharma M, Vijayaraghavan R, Gautam A. DRDE-07 and its analogues as promising cytoprotectants to nitrogen mustard (HN-2)--an alkylating anticancer and chemical warfare agent. Toxicol Lett. 2009 Aug 10;188(3):243-50. Epub 2009 May 3. PubMed PMID: 19397960.

2: Armand JP, Ribrag V, Harrousseau JL, Abrey L. Reappraisal of the use of procarbazine in the treatment of lymphomas and brain tumors. Ther Clin Risk Manag. 2007 Jun;3(2):213-24. PubMed PMID: 18360630; PubMed Central PMCID: PMC1936303.

3: Bartzatt R. Alkylation activity and molecular properties of two antineoplastic agents that utilise indometacin and a conjugate of aspirin with 2-aminonicotinic acid to transport nitrogen mustard groups. Drugs R D. 2007;8(6):363-72. PubMed PMID: 17963427.

4: Zhang X, Ling MT, Wong YC, Wang X. Evidence of a novel antiapoptotic factor: role of inhibitor of differentiation or DNA binding (Id-1) in anticancer drug-induced apoptosis. Cancer Sci. 2007 Mar;98(3):308-14. PubMed PMID: 17214747.

5: He D, Zhang D, Wei G, Lin T, Li X. Cytoskeleton vimentin disruption of mouse sertoli cells injured by nitrogen mustard in vitro. J Androl. 2007 May-Jun;28(3):389-96. Epub 2006 Dec 27. PubMed PMID: 17192600.

6: Dutta S, Abe H, Aoyagi S, Kibayashi C, Gates KS. DNA damage by fasicularin. J Am Chem Soc. 2005 Nov 2;127(43):15004-5. PubMed PMID: 16248621.

7: Eklund JW, Trifilio S, Mulcahy MF. Chemotherapy dosing in the setting of liver dysfunction. Oncology (Williston Park). 2005 Jul;19(8):1057-63; discussion 1063-4, 1069. Review. PubMed PMID: 16131047.

8: Guo CC, Tong RB, Li KL. Chloroalkyl piperazine and nitrogen mustard porphyrins: synthesis and anticancer activity. Bioorg Med Chem. 2004 May 1;12(9):2469-75. PubMed PMID: 15080942.

9: Rapp M, Giraud I, Maurizis JC, Galmier MJ, Madelmont JC. Synthesis and in vivo biodisposition of [14C]-quaternary ammonium-melphalan conjugate, a potential cartilage-targeted alkylating drug. Bioconjug Chem. 2003 Mar-Apr;14(2):500-6. PubMed PMID: 12643763.

10: Kapuscinski J, Ardelt B, Piosik J, Zdunek M, Darzynkiewicz Z. The modulation of the DNA-damaging effect of polycyclic aromatic agents by xanthines. Part I. Reduction of cytostatic effects of quinacrine mustard by caffeine. Biochem Pharmacol. 2002 Feb 15;63(4):625-34. PubMed PMID: 11992630.

11: Barret JM, Cadou M, Hill BT. Inhibition of nucleotide excision repair and sensitisation of cells to DNA cross-linking anticancer drugs by F 11782, a novel fluorinated epipodophylloid. Biochem Pharmacol. 2002 Jan 15;63(2):251-8. PubMed PMID: 11841800.

12: Tabaru K, Konno T, Oda T, Nagamitsu A, Ishimaru Y, Kitamura N. Treatment of VX2 carcinoma implanted in the liver with arterial and intraperitoneal administration of oily anticancer agents. Cancer Chemother Pharmacol. 2001;47(2):149-54. PubMed PMID: 11269741.

13: Lishner M, Manor Y, Kitay-Cohen Y, Avishay AE. Association between alopecia and response to aggressive chemotherapy in patients with Hodgkin's disease. Med Hypotheses. 1999 Nov;53(5):447-9. PubMed PMID: 10616048.

14: McHugh PJ, Gill RD, Waters R, Hartley JA. Excision repair of nitrogen mustard-DNA adducts in Saccharomyces cerevisiae. Nucleic Acids Res. 1999 Aug 15;27(16):3259-66. PubMed PMID: 10454632; PubMed Central PMCID: PMC148558.

15: Canitrot Y, Cazaux C, Fréchet M, Bouayadi K, Lesca C, Salles B, Hoffmann JS. Overexpression of DNA polymerase beta in cell results in a mutator phenotype and a decreased sensitivity to anticancer drugs. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12586-90. PubMed PMID: 9770529; PubMed Central PMCID: PMC22874.

16: Antoine M, Fabris D, Fenselau C. Covalent sequestration of the nitrogen mustard mechlorethamine by metallothionein. Drug Metab Dispos. 1998 Sep;26(9):921-6. PubMed PMID: 9733672.

17: Meurman JH, Laine P, Keinànen S, Pyrhönen S, Teerenhovi L, Lindqvist C. Five-year follow-up of saliva in patients treated for lymphomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997 Apr;83(4):447-52. PubMed PMID: 9127375.

18: Son K, Huang L. Factors influencing the drug sensitization of human tumor cells for in situ lipofection. Gene Ther. 1996 Jul;3(7):630-4. PubMed PMID: 8818651.

19: Skretkowicz J, Sekulska M, Danilewicz M, Wagrowska-Danilewicz M, Polakowski P. Effect of some anticancer drugs and combined chemotherapy on renal toxicity. Biol Signals. 1996 Jan-Feb;5(1):51-8. PubMed PMID: 8739323.

20: Lunel-Orsini C, Buttin G, De Saint Vincent BR. A glutathione depletion selectively imposed on mu glutathione S-transferase overproducing cells increases nitrogen mustard toxicity. Biochem Pharmacol. 1995 Jan 31;49(3):329-38. PubMed PMID: 7857320.

21: Fox ME, Feldman BJ, Chu G. A novel role for DNA photolyase: binding to DNA damaged by drugs is associated with enhanced cytotoxicity in Saccharomyces cerevisiae. Mol Cell Biol. 1994 Dec;14(12):8071-7. PubMed PMID: 7969145; PubMed Central PMCID: PMC359345.

22: Hofmann J, O'Connor PM, Jackman J, Schubert C, Ueberall F, Kohn KW, Grunicke H. The protein kinase C inhibitor ilmofosine (BM 41 440) arrests cells in G2 phase and suppresses CDC2 kinase activation through a mechanism different from that of DNA damaging agents. Biochem Biophys Res Commun. 1994 Mar 15;199(2):937-43. PubMed PMID: 8135843.

23: Bhattacharya S, Ganguly C, Sanyal U, Das S. Evaluation of phthalmustine, a new anticancer compound. I. Effect on Dalton's ascitic lymphoma in mice. Neoplasma. 1994;41(1):35-8. PubMed PMID: 8202193.

24: Fernández AG, Puig J, Beleta J, Doménech T, Bou J, Berga P, Gristwood RW, Roberts DJ. Pancopride, a potent and long-acting 5-HT3 receptor antagonist, is orally effective against anticancer drug-evoked emesis. Eur J Pharmacol. 1992 Nov 10;222(2-3):257-64. PubMed PMID: 1451737.

25: Laine P, Meurman JH, Tenovuo J, Murtomaa H, Lindqvist C, Pyrhönen S, Teerenhovi L. Salivary flow and composition in lymphoma patients before, during and after treatment with cytostatic drugs. Eur J Cancer B Oral Oncol. 1992 Oct;28B(2):125-8. PubMed PMID: 1284874.

26: Khan S, Ramwani JJ, O'Brien PJ. Hepatocyte toxicity of mechlorethamine and other alkylating anticancer drugs. Role of lipid peroxidation. Biochem Pharmacol. 1992 May 8;43(9):1963-7. PubMed PMID: 1596284.

27: Caldecott K, Jeggo P. Cross-sensitivity of gamma-ray-sensitive hamster mutants to cross-linking agents. Mutat Res. 1991 Sep;255(2):111-21. PubMed PMID: 1922147.

28: Cummings J, MacLellan A, Smyth JF, Farmer PB. Determination of reactive nitrogen mustard anticancer drugs in plasma by high-performance liquid chromatography using derivatization. Anal Chem. 1991 Aug 1;63(15):1514-9. PubMed PMID: 1952082.

29: Ambaye RY, Indap MA. Influence of N-(o-methoxyphenyl)-maleimide on 5-fluorouracil cytotoxicity in Ehrlich (ascites) carcinoma. Cancer Lett. 1991 Apr;57(1):21-6. PubMed PMID: 1902758.

30: Millward MJ, Cohney SJ, Byrne MJ, Ryan GF. Pulmonary toxicity following MOPP chemotherapy. Aust N Z J Med. 1990 Jun;20(3):245-8. Review. PubMed PMID: 2196871.

31: Dorr RT. Antidotes to vesicant chemotherapy extravasations. Blood Rev. 1990 Mar;4(1):41-60. Review. PubMed PMID: 2182147.

32: Dorr RT, Soble M, Alberts DS. Efficacy of sodium thiosulfate as a local antidote to mechlorethamine skin toxicity in the mouse. Cancer Chemother Pharmacol. 1988;22(4):299-302. PubMed PMID: 3168143.

33: Aida T, Bodell WJ. [Anticancer drug induced sister chromatid exchange and correlation to cell survival in human brain tumor cells]. No To Shinkei. 1987 Mar;39(3):235-41. Japanese. PubMed PMID: 3472531.

34: Prokopowicz J, Kemona H, Wysocka J, Kiluk S. Serum lysozyme activity in patients with Hodgkin's disease undergoing chemotherapy. Folia Haematol Int Mag Klin Morphol Blutforsch. 1987;114(3):338-47. PubMed PMID: 2444507.

35: Fingert HJ, Chang JD, Pardee AB. Cytotoxic, cell cycle, and chromosomal effects of methylxanthines in human tumor cells treated with alkylating agents. Cancer Res. 1986 May;46(5):2463-7. PubMed PMID: 3084068.

36: Cantrell JE Jr, Green D, Schein PS. Antitumor activity and bone marrow toxicity of aminoglucose mustard anticancer agents in mice. Cancer Res. 1986 May;46(5):2340-3. PubMed PMID: 2938728.

37: Takeda M, Hosaka M, Kitajima N, Noguchi K, Fujii H, Oshima H, Harada M. [Effect of anticancer agents on rat prostate. Evaluation of organ weight, histological finding and 5 alpha-reductase activities]. Hinyokika Kiyo. 1985 Jan;31(1):71-80. Japanese. PubMed PMID: 2581430.

38: Yamanaka H, Shida K. [Pharmacology and metabolism of a new therapeutic drug for prostatic cancer "Estracyt"]. Gan To Kagaku Ryoho. 1984 Mar;11(3):537-44. Japanese. PubMed PMID: 6422861.

39: Bonadonna G, Santoro A, Viviani S, Lombardi C, Ragni G. Gonadal damage in Hodgkin's disease from cancer chemotherapeutic regimens. Arch Toxicol Suppl. 1984;7:140-5. PubMed PMID: 6083763.

40: Medoff G, Valeriote F, Dieckman J. Potentiation of anticancer agents by amphotericin B. J Natl Cancer Inst. 1981 Jul;67(1):131-5. PubMed PMID: 6942183.

41: Neidhart JA, Gagen M, Young D, Wilson HE. Specific antiemetics for specific cancer chemotherapeutic agents: haloperidol versus benzquinamide. Cancer. 1981 Mar 15;47(6):1439-43. PubMed PMID: 7013968.

42: Baba T, Nishikawa K. Effective combination of anticancer drug with its antidote for chemotherapy of hepatic metastasis. Gann. 1980 Feb;71(1):157-8. PubMed PMID: 7380134.

43: Fleer R, Brendel M. Formation and fate of cross-links induced by polyfunctional anticancer drugs in yeast. Mol Gen Genet. 1979 Oct 2;176(1):41-52. PubMed PMID: 396449.

44: Kidera Y, Kamura T, Aoki K, Kimura M, Baba T. [Protective effects of general hypothermia on side effects of anticancer drugs in the "regional hyperthermic chemotherapy combined with temporary interruption of local blood-circulation" (author's transl)]. Fukuoka Igaku Zasshi. 1976 Sep;67(9):325-30. Japanese. PubMed PMID: 1033893.

45: Koga H. [The studies on anerobic glycolysis and the inhibition of lactic acid production in Ehrlich's ascites carcinoma by anticancer agents]. Kumamoto Igakkai Zasshi. 1971 Feb 25;45(2):169-99. Japanese. PubMed PMID: 5109085.

46: Sudo I. [Histochemical and biochemical studies on the effects of anticancer agents on glycogen metabolism in AH13 ascites hepatoma]. Kumamoto Igakkai Zasshi. 1969 Apr 25;43(4):277-96. Japanese. PubMed PMID: 4308494.

47: Cambanis A, Dobre V, Niculescu-Duvăz I. Potential anticancer agents. V. New aromatic nitrogen mustards related to 3-[N,N-bis(2-chloroethyl)amino]-4-methylbenzoic acid. J Med Chem. 1969 Jan;12(1):161-4. PubMed PMID: 5763014.

48: Reboul AR, Lewest G. [Modalities and results of anticancer polychemotherapy in 73 cases of advanced broncho-pleuro-pulmonary cancer]. Poumon Coeur. 1968;24(1):117-23. French. PubMed PMID: 5661797.

49: Everett J. Walker carcinosarcoma 256 in study of anticancer agents. II. Results. Cancer Res. 1966 Aug;26(8 Pt 2):942-9. PubMed PMID: 4224206.

50: TOKUYAMA E, MIZOTA S, SATOU H, TSUNEMATSU T, MATSUZAKI A. [FUNDAMENTAL STUDIES ON THE ADMINISTRATION OF MIXED ANTICANCER AGENTS.]. Gan No Rinsho. 1965 May;11:256-61. Japanese. PubMed PMID: 14296333.

51: ROUSSELOT LM, GROSSI CE, SLATTERY J, ROSSI P, RUZICKA FF Jr, PRYTZ B. SELECTIVE CONCENTRATION OF ANTICANCER DRUGS IN THE LIVER: HEPATIC-ARTERY INFUSION AND INDUCED HEPATIC OUTFLOW BLOCK. JAMA. 1965 Mar 1;191:707-10. PubMed PMID: 14245509.

52: ITO T. [HEMATOLOGICAL AND HISTOLOGICAL STUDIES IN THE OFFSPRINGS OF WISTAR STRAIN ALBINO RATS TREATED WITH ANTICANCER DRUGS OF X-RAY IRRADIATION. I. HEMATOLOGICAL AND HISTOLOGICAL OBSERVATIONS ON WISTAR STRAIN RATS ADMINISTERED WITH NITROGEN MUSTARD-N-OXIDE.]. Naika Hokan. 1965 Feb;12:69-81. Japanese. PubMed PMID: 14306288.

53: ROUSSELOT LM, GROSSI CE, SLATTERY J, ROSSI P, CONTE AJ, RUZICKA FF Jr. TEMPORARY HEPATIC OUTFLOW BLOCK WITH HEPATIC ARTERY PERFUSION BY ANTICANCER AGENTS. Surg Gynecol Obstet. 1964 Jun;118:1295-304. PubMed PMID: 14177846.

54: FUJII M. STUDIES ON THE HEME SYNTHESIS BY BONE MARROW CELLS IN VITRO AND IN VIVO WITH 2-14C-GLYCINE. III. EFFECTS OF VITAMINS AND ANTICANCER AGENTS ON HEME SYNTHESIS BY RABBIT BONE MARROW CELLS IN VITRO. Naika Hokan. 1964 Mar;11:111-5. PubMed PMID: 14163641.

55: KNOCK FE. NEWER ANTICANCER AGENTS. Med Clin North Am. 1964 Mar;48:501-27. Review. PubMed PMID: 14151253.

56: SAKAI S, SAITO G, SUGAYAMA J, KAMASUKA T, TAKADA S, TAKANO T. [ON THE ANTICANCER ACTION OF BAMBOO EXTRACT.]. J Antibiot B. 1963 Dec;16:387-91. Japanese. PubMed PMID: 14117204.

57: ARON E, COMBESCOT C, GROUSSIN P. [VALUE OF PROLONGED TREATMENT BY LOW DRUG DOSES IN ANTICANCER CHEMOTHERAPY.]. Therapie. 1963 Nov-Dec;18:1331-8. French. PubMed PMID: 14117529.

58: HENDERSON IW, SHAH RC, SCHOOP HD, MERRILL K Jr, SCOTT ME. Local toxicity in regional perfusion with anticancer compounds. J Surg Res. 1963 May;3:162-70. PubMed PMID: 13953696.

59: MCNAIR TJ, WIBIN FA, HOPPE ET, SCHMIDT JL, DEPEYSTER JA. Antitumor action of several new piperazine derivatives compared to certain standard anticancer agents. J Surg Res. 1963 May;3:130-6. PubMed PMID: 13932216.

60: STALEY CJ, KUKRAL JC, PRESTON FW. Effect of anticancer drugs on experimental wound healing. Surg Forum. 1962;13:35-6. PubMed PMID: 13983304.