Details of the Drug

General Information of Drug (ID: DM0CVXA)

• Drug Name: Mechlorethamine
• Synonyms: Antimit; Carolysine; Caryolysin; Caryolysine; Chlorethazine; Chlormethine; Cloramin; Clormetina; Dichloren; Embechine; Embichin; MBA; Mebichloramine; Mechlorethanamine; Mechloroethamine; Mecloretamina; Mustargen; Mustine; Mutagen; Nitrogranulogen; Thyldiethylamine; Dichlor amine; Me chloroethamine; Mecloretamina [Italian]; Mustine note; Nitrogen mustard; HN2; T 1024; TL 146; Chloramine (the nitrogen mustard); Chlormethine (INN); Chlormethine [INN:BAN]; Chlormethinum [INN-Latin]; Clormetina [INN-Spanish]; ENT-25294; HN-2; IBS-L0033631; Mustargen (TN); N-Lost; N-Methyl lost; Stickstofflost (ebewe); T-1024; Bis(2-chloroethyl)methylamine; Bis(beta-chloroethyl) methylamine; Bis(beta-chloroethyl)methylamine; Di(2-chloroethyl)methylamine; Methylbis(2-chloroethyl)amine; Methylbis(beta-chloroethyl)amine; Methyldi(2-chloroethyl)amine; N-Methyl-lost; N-Methyl-lost [German]; Nitrogen mustard (HN-2); Mitoxine (*Hydrochloride*); N,N-Di(chloroethyl)methylamine; N-Methyl-bis-chloraethylamin; N-Methyl-bis-chloraethylamin [German]; Nitol (*Hydrochloride*); Stickstofflost (*Hydrochloride*); N,N-Bis(2-chloroethyl)methylamine; N-Methyl-bis(2-chloroethyl)amine; N-Methyl-bis(beta-chloroethyl)amine; Beta,beta'-Dichlorodiethyl-N-methylamine; N-Methyl-2,2'-dichlorodiethylamine; N,N-Bis(2-chloroethyl)-N-methylamine; 1,5-Dichloro-3-methyl-3-azapentane hydrochloride; 2,2'-Dichloro-N-me; 2,2'-Dichloro-N-methyldiethylamine; 2,2'-Dichlorodiethyl-methylamine; 2-Chloro-N-(2-chloroethyl)-N-methylethanamine

Indication

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[1]
Lung cancer	2C25.0	Approved	[1]
Mycosis fungoides	2B01	Approved	[1]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[1]
Small lymphocytic lymphoma	2A82.0	Approved	[1]
T-cell lymphoma	2A90	Approved	[2]
Hodgkin lymphoma	2B30	Phase 3	[3]
Classic Hodgkin lymphoma	N.A.	Investigative	[1]

• Therapeutic Class: Anticancer Agents
• Affected Organisms: Humans and other mammals
• ATC Code:
  L01AA05: Mechlorethamine
  L01AA: Nitrogen mustard analogues
  L01A: ALKYLATING AGENTS
  L01: ANTINEOPLASTIC AGENTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 156.05
  Logarithm of the Partition Coefficient (xlogp); 0.9
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property: Half-life: The concentration or amount of drug in body reduced by one-half in 15 minutes [4]
• Chemical Identifiers:
  Formula: C5H11Cl2N
  IUPAC Name: 2-chloro-N-(2-chloroethyl)-N-methylethanamine
  Canonical SMILES: CN(CCCl)CCCl
  InChI: InChI=1S/C5H11Cl2N/c1-8(4-2-6)5-3-7/h2-5H2,1H3
  InChIKey: HAWPXGHAZFHHAD-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4033
  ChEBI ID: CHEMBL28925
  CAS Number: 51-75-2
  UNII: 50D9XSG0VR
  DrugBank ID: DB00888
  TTD ID: D03SSE
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
• Drug ADMET Endpoint Profile (DAE)NEW: Click to Jump to the Detailed DAE Information of This Drug
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Intercalator	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Gene/Protein Processing	[6]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Gene/Protein Processing	[7]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Gene/Protein Processing	[8]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Gene/Protein Processing	[9]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Gene/Protein Processing	[10]
Thioredoxin	OT6XU6VW	THIO_HUMAN	Gene/Protein Processing	[11]
Thioredoxin reductase 2, mitochondrial	OTZQQC3T	TRXR2_HUMAN	Gene/Protein Processing	[12]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Gene/Protein Processing	[7]
Transcription factor JunB (JUNB)	OTG2JXV5	JUNB_HUMAN	Gene/Protein Processing	[7]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Gene/Protein Processing	[7]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Mechlorethamine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Mechlorethamine and Roflumilast.	Asthma [CA23]	[13]
Ofloxacin	DM0VQN3	Minor	Decreased absorption of Mechlorethamine due to intestinal mucosa variation caused by Ofloxacin.	Bacterial infection [1A00-1C4Z]	[14]
Sparfloxacin	DMB4HCT	Minor	Decreased absorption of Mechlorethamine due to intestinal mucosa variation caused by Sparfloxacin.	Bacterial infection [1A00-1C4Z]	[14]
Gemifloxacin	DMHT34O	Minor	Decreased absorption of Mechlorethamine due to intestinal mucosa variation caused by Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[14]
Norfloxacin	DMIZ6W2	Minor	Decreased absorption of Mechlorethamine due to intestinal mucosa variation caused by Norfloxacin.	Bacterial infection [1A00-1C4Z]	[14]
ABT-492	DMJFD2I	Minor	Decreased absorption of Mechlorethamine due to intestinal mucosa variation caused by ABT-492.	Bacterial infection [1A00-1C4Z]	[14]
Levofloxacin	DMS60RB	Minor	Decreased absorption of Mechlorethamine due to intestinal mucosa variation caused by Levofloxacin.	Bacterial infection [1A00-1C4Z]	[14]
Lomefloxacin	DMVRH9C	Minor	Decreased absorption of Mechlorethamine due to intestinal mucosa variation caused by Lomefloxacin.	Bacterial infection [1A00-1C4Z]	[14]
Teriflunomide	DMQ2FKJ	Major	Additive immunosuppressive effects by the combination of Mechlorethamine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[15]
Penbutolol	DM4ES8F	Minor	Increased plasma concentration of Mechlorethamine and Penbutolol due to competitive binding of plasma proteins.	Hypertension [BA00-BA04]	[16]
Denosumab	DMNI0KO	Moderate	Additive immunosuppressive effects by the combination of Mechlorethamine and Denosumab.	Low bone mass disorder [FB83]	[17]
Thalidomide	DM70BU5	Major	Additive thrombogenic effects by the combination of Mechlorethamine and Thalidomide.	Multiple myeloma [2A83]	[18]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Mechlorethamine and Tecfidera.	Multiple sclerosis [8A40]	[19]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Mechlorethamine and Siponimod.	Multiple sclerosis [8A40]	[20]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Mechlorethamine and Fingolimod.	Multiple sclerosis [8A40]	[21]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Mechlorethamine and Ocrelizumab.	Multiple sclerosis [8A40]	[22]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Mechlorethamine and Ozanimod.	Multiple sclerosis [8A40]	[13]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Mechlorethamine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[23]
Gatifloxacin	DMSL679	Minor	Decreased absorption of Mechlorethamine due to intestinal mucosa variation caused by Gatifloxacin.	Respiratory infection [CA07-CA4Z]	[14]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Mechlorethamine and Canakinumab.	Rheumatoid arthritis [FA20]	[24]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Mechlorethamine and Rilonacept.	Rheumatoid arthritis [FA20]	[24]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Mechlorethamine and Golimumab.	Rheumatoid arthritis [FA20]	[25]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Mechlorethamine when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[26]
Azathioprine	DMMZSXQ	Moderate	Additive immunosuppressive effects by the combination of Mechlorethamine and Azathioprine.	Transplant rejection [NE84]	[20]
Ganciclovir	DM1MBYQ	Moderate	Additive myelosuppressive effects by the combination of Mechlorethamine and Ganciclovir.	Virus infection [1A24-1D9Z]	[20]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Mechlorethamine and Valganciclovir.	Virus infection [1A24-1D9Z]	[20]

References

• [1] Mechlorethamine FDA Label
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7218).
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Proteomic analysis of DNA-protein cross-linking by antitumor nitrogen mustards. Chem Res Toxicol. 2009 Jun;22(6):1151-62.
• [6] Increased expression of VDAC1 sensitizes carcinoma cells to apoptosis induced by DNA cross-linking agents. Biochem Pharmacol. 2012 May 1;83(9):1172-82. doi: 10.1016/j.bcp.2012.01.017. Epub 2012 Jan 21.
• [7] Nitrogen mustard prevents transport of Fra-1 into the nucleus to promote c-Fos- and FosB-dependent IL-8 induction in injured mouse epidermis. Toxicol Lett. 2020 Feb 1;319:256-263. doi: 10.1016/j.toxlet.2019.10.006. Epub 2019 Oct 19.
• [8] Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard. Am J Dermatopathol. 1998 Feb;20(1):22-8. doi: 10.1097/00000372-199802000-00005.
• [9] S100P is selectively upregulated in tumor cell lines challenged with DNA cross-linking agents. Leuk Res. 2005 Oct;29(10):1181-90. doi: 10.1016/j.leukres.2005.03.012.
• [10] Down-regulation of HER-2 expression in human breast cancer cell HBC-4 and ZR75-1 by nitrogen-mustard-N-oxide. Kobe J Med Sci. 2007;53(4):135-42.
• [11] Thioredoxin Cross-Linking by Nitrogen Mustard in Lung Epithelial Cells: Formation of Multimeric Thioredoxin/Thioredoxin Reductase Complexes and Inhibition of Disulfide Reduction. Chem Res Toxicol. 2015 Nov 16;28(11):2091-103. doi: 10.1021/acs.chemrestox.5b00194. Epub 2015 Oct 19.
• [12] Cross-linking of thioredoxin reductase by the sulfur mustard analogue mechlorethamine (methylbis(2-chloroethyl)amine) in human lung epithelial cells and rat lung: selective inhibition of disulfide reduction but not redox cycling. Chem Res Toxicol. 2014 Jan 21;27(1):61-75. doi: 10.1021/tx400329a. Epub 2013 Dec 9.
• [13] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [14] Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
• [15] Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
• [16] Aguirre C, Rodriguez-Sasiain JM, Calvo R "Decrease in penbutolol protein binding as a consequence of treatment with some alkylating agents." Cancer Chemother Pharmacol 34 (1994): 86-8. [PMID: 8174208]
• [17] Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
• [18] Figg WD, Arlen P, Gulley J, et al. "A randomized phase II trial of docetaxel (taxotere) plus thalidomide in androgen-independent prostate cancer." Semin Oncol 28(4 Suppl 15) (2001): 62-6. [PMID: 11685731]
• [19] Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
• [20] Cerner Multum, Inc. "Australian Product Information.".
• [21] Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
• [22] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
• [23] Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
• [24] Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
• [25] Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
• [26] CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]