General Information of Drug Combination (ID: DCIGY58)

Drug Combination Name
Mechlorethamine DFN-15
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Mechlorethamine   DM0CVXA DFN-15   DM3BF9B
Small molecular drug N.A.
High-throughput Screening Result Testing Cell Line: SW-620
Zero Interaction Potency (ZIP) Score: 3.32
Bliss Independence Score: 10.25
Loewe Additivity Score: 4.82
LHighest Single Agent (HSA) Score: 4.82

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Mechlorethamine
Disease Entry ICD 11 Status REF
Chronic myelogenous leukaemia 2A20.0 Approved [2]
Lung cancer 2C25.0 Approved [2]
Mycosis fungoides 2B01 Approved [2]
Primary cutaneous T-cell lymphoma N.A. Approved [2]
Small lymphocytic lymphoma 2A82.0 Approved [2]
T-cell lymphoma 2A90 Approved [3]
Hodgkin lymphoma 2B30 Phase 3 [4]
Classic Hodgkin lymphoma N.A. Investigative [2]
Mechlorethamine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Intercalator [8]
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Mechlorethamine Interacts with 19 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Decreases Expression [9]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Decreases Activity [10]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [11]
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Activity [12]
Glutathione S-transferase A2 (GSTA2) OTW7UB1H GSTA2_HUMAN Increases Expression [13]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [11]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [14]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Activity [12]
Transcription factor JunB (JUNB) OTG2JXV5 JUNB_HUMAN Increases Expression [11]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Increases Expression [11]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Increases Stability [12]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Increases Activity [12]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Expression [15]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [16]
Caspase-2 (CASP2) OTUDYSPP CASP2_HUMAN Increases Activity [14]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [14]
Laminin subunit gamma-2 (LAMC2) OTJMTM72 LAMC2_HUMAN Decreases Expression [17]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Increases Expression [18]
Transient receptor potential cation channel subfamily A member 1 (TRPA1) OTRDIR5M TRPA1_HUMAN Increases Response To Substance [19]
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⏷ Show the Full List of 19 DOT(s)
Indication(s) of DFN-15
Disease Entry ICD 11 Status REF
Migraine 8A80 Phase 3 [5]

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Plasma cell myeloma DCQRZMV RPMI-8226 Investigative [20]
Adenocarcinoma DCCP1DU HCT116 Investigative [1]
Large cell lung carcinoma DC705YT NCI-H460 Investigative [1]
Minimally invasive lung adenocarcinoma DC0ACJE NCI-H322M Investigative [1]
Prostate carcinoma DCH92KF PC-3 Investigative [1]
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References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
2 Mechlorethamine FDA Label
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 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).
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 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.
7 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.
8 Proteomic analysis of DNA-protein cross-linking by antitumor nitrogen mustards. Chem Res Toxicol. 2009 Jun;22(6):1151-62.
9 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.
10 Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes. Chem Res Toxicol. 2022 Apr 18;35(4):636-650. doi: 10.1021/acs.chemrestox.1c00420. Epub 2022 Mar 21.
11 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.
12 G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2 and cyclin B1/cdc2-kinase complexes differently. J Biol Chem. 1993 Apr 15;268(11):8298-308.
13 Overexpression of GSTA2 protects against cell cycle arrest and apoptosis induced by the DNA inter-strand crosslinking nitrogen mustard, mechlorethamine. J Cell Biochem. 2005 May 15;95(2):339-51. doi: 10.1002/jcb.20440.
14 Inhibition of caspase-dependent mitochondrial permeability transition protects airway epithelial cells against mustard-induced apoptosis. Apoptosis. 2006 Sep;11(9):1545-59. doi: 10.1007/s10495-006-8764-1.
15 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.
16 Ebselen reduces the toxicity of mechlorethamine in A-431 cells via inhibition of apoptosis. J Biochem Mol Toxicol. 2013 Jun;27(6):313-22. doi: 10.1002/jbt.21490. Epub 2013 May 6.
17 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.
18 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.
19 Activation of the human TRPA1 channel by different alkylating sulfur and nitrogen mustards and structurally related chemotherapeutic drugs. Toxicol Lett. 2023 Mar 1;376:51-59. doi: 10.1016/j.toxlet.2023.01.007. Epub 2023 Jan 21.
20 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.