General Information of Drug Combination (ID: DCHRAF0)

Drug Combination Name
Mechlorethamine Pomalidomide
Indication
Disease Entry Status REF
Childhood T acute lymphoblastic leukemia Investigative [1]
Component Drugs Mechlorethamine   DM0CVXA Pomalidomide   DMTGBAX
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: CCRF-CEM
Zero Interaction Potency (ZIP) Score: 6.61
Bliss Independence Score: 8.92
Loewe Additivity Score: 4.33
LHighest Single Agent (HSA) Score: 9.55

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 [9]
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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 [10]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Decreases Activity [11]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [12]
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Activity [13]
Glutathione S-transferase A2 (GSTA2) OTW7UB1H GSTA2_HUMAN Increases Expression [14]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [12]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [15]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Activity [13]
Transcription factor JunB (JUNB) OTG2JXV5 JUNB_HUMAN Increases Expression [12]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Increases Expression [12]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Increases Stability [13]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Increases Activity [13]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Expression [16]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [17]
Caspase-2 (CASP2) OTUDYSPP CASP2_HUMAN Increases Activity [15]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [15]
Laminin subunit gamma-2 (LAMC2) OTJMTM72 LAMC2_HUMAN Decreases Expression [18]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Increases Expression [19]
Transient receptor potential cation channel subfamily A member 1 (TRPA1) OTRDIR5M TRPA1_HUMAN Increases Response To Substance [20]
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⏷ Show the Full List of 19 DOT(s)
Indication(s) of Pomalidomide
Disease Entry ICD 11 Status REF
Plasma cell myeloma 2A83.1 Approved [5]
Systemic sclerosis 4A42 Approved [6]
Pomalidomide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Angiogenesis/myeloma cell growth (AMCG) TTDIBYJ NOUNIPROTAC Modulator [21]
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Pomalidomide Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [22]
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Pomalidomide Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [23]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [24]
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Pomalidomide Interacts with 27 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Oxidation [25]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Decreases Secretion [26]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Secretion [26]
Granulocyte colony-stimulating factor (CSF3) OT9GC6TP CSF3_HUMAN Increases Secretion [26]
Fibroblast growth factor receptor 1 (FGFR1) OT4GLCXW FGFR1_HUMAN Decreases Expression [27]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [26]
Erythroid transcription factor (GATA1) OTX1R7O1 GATA1_HUMAN Decreases Expression [26]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Decreases Expression [26]
Transcription factor PU.1 (SPI1) OTVCA1D0 SPI1_HUMAN Increases Expression [26]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [26]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Affects Expression [27]
Endothelial transcription factor GATA-2 (GATA2) OTBP2QQ2 GATA2_HUMAN Decreases Expression [26]
Rhombotin-2 (LMO2) OTCC370G RBTN2_HUMAN Decreases Expression [26]
Interleukin-13 (IL13) OTI4YS3Y IL13_HUMAN Decreases Secretion [26]
DNA-binding protein inhibitor ID-1 (ID1) OTKGNZN5 ID1_HUMAN Increases Expression [26]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Increases Expression [26]
CCAAT/enhancer-binding protein delta (CEBPD) OTNBIPMY CEBPD_HUMAN Increases Expression [26]
DNA-binding protein inhibitor ID-2 (ID2) OT0U1D53 ID2_HUMAN Increases Expression [26]
Krueppel-like factor 1 (KLF1) OT1FK08U KLF1_HUMAN Decreases Expression [26]
CCAAT/enhancer-binding protein epsilon (CEBPE) OTKZA25M CEBPE_HUMAN Increases Expression [26]
Transcription factor NF-E2 45 kDa subunit (NFE2) OTLM94BI NFE2_HUMAN Decreases Expression [26]
Zinc finger protein Gfi-1b (GFI1B) OTRDW8YO GFI1B_HUMAN Decreases Expression [26]
Zinc finger protein Gfi-1 (GFI1) OT9HB9H8 GFI1_HUMAN Increases Expression [26]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [28]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Oxidation [25]
Cytochrome P450 2J2 (CYP2J2) OTJBTEH8 CP2J2_HUMAN Increases Oxidation [25]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [29]
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⏷ Show the Full List of 27 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult acute myeloid leukemia DCFHBBU HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DCMEMC7 MOLT-4 Investigative [1]
Clear cell renal cell carcinoma DCOUD09 786-0 Investigative [1]
Clear cell renal cell carcinoma DCWFYJN CAKI-1 Investigative [1]
Glioblastoma DCTLYTO SNB-75 Investigative [1]
Glioma DCMELCS SF-295 Investigative [1]
Plasma cell myeloma DC1NRWG RPMI-8226 Investigative [1]
Renal cell carcinoma DCR8PC8 SN12C Investigative [1]
Carcinoma DCTAJ57 RXF 393 Investigative [30]
Colon carcinoma DCCASKI KM12 Investigative [30]
Adenocarcinoma DCTEOC1 HCT116 Investigative [31]
Adenocarcinoma DC94RWB HCC-2998 Investigative [31]
Amelanotic melanoma DCR9RM2 M14 Investigative [31]
High grade ovarian serous adenocarcinoma DCZD9PK OVCAR-4 Investigative [31]
High grade ovarian serous adenocarcinoma DC39MQT NCI\\/ADR-RES Investigative [31]
Lung adenocarcinoma DCKI64Q EKVX Investigative [31]
Malignant melanoma DCASP9E UACC62 Investigative [31]
Non-small cell lung carcinoma DCKSJA8 HOP-92 Investigative [31]
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⏷ Show the Full List of 18 DrugCom(s)

References

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2 Mechlorethamine FDA Label
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5 Pomalidomide FDA Label
6 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: 7348).
7 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.
8 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.
9 Proteomic analysis of DNA-protein cross-linking by antitumor nitrogen mustards. Chem Res Toxicol. 2009 Jun;22(6):1151-62.
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 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.
12 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.
13 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.
14 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.
15 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.
16 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.
17 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.
18 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.
19 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.
20 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.
21 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
22 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08910)
23 Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78.
24 Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72.
25 Human cytochrome P450 oxidation of 5-hydroxythalidomide and pomalidomide, an amino analogue of thalidomide. Chem Res Toxicol. 2014 Jan 21;27(1):147-56. doi: 10.1021/tx4004215. Epub 2013 Dec 24.
26 Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood. 2005 May 15;105(10):3833-40. doi: 10.1182/blood-2004-03-0828. Epub 2004 Aug 3.
27 Thalidomide and Its Analogs Differentially Target Fibroblast Growth Factor Receptors: Thalidomide Suppresses FGFR Gene Expression while Pomalidomide Dampens FGFR2 Activity. Chem Res Toxicol. 2019 Apr 15;32(4):589-602. doi: 10.1021/acs.chemrestox.8b00286. Epub 2019 Mar 15.
28 Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife. 2018 Aug 1;7:e38430. doi: 10.7554/eLife.38430.
29 A Dual Color Immunohistochemistry Assay for Measurement of Cereblon in Multiple Myeloma Patient Samples. Appl Immunohistochem Mol Morphol. 2016 Nov/Dec;24(10):695-702. doi: 10.1097/PAI.0000000000000246.
30 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
31 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.