General Information of Drug Combination (ID: DCVQ6ID)

Drug Combination Name
Lenalidomide Mercaptopurine
Indication
Disease Entry Status REF
Minimally invasive lung adenocarcinoma Investigative [1]
Component Drugs Lenalidomide   DM6Q7U4 Mercaptopurine   DMTM2IK
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: NCI-H322M
Zero Interaction Potency (ZIP) Score: 2.78
Bliss Independence Score: 8.79
Loewe Additivity Score: 5.35
LHighest Single Agent (HSA) Score: 5.35

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Lenalidomide
Disease Entry ICD 11 Status REF
Adult T-cell leukemia/lymphoma N.A. Approved [2]
Advanced cancer 2A00-2F9Z Approved [2]
Complex regional pain syndrome type 1 N.A. Approved [2]
Hepatosplenic T-cell lymphoma N.A. Approved [2]
Large granular lymphocytic leukemia 2A90.1 Approved [2]
Leukemia N.A. Approved [2]
MALT lymphoma N.A. Approved [2]
Multiple myeloma 2A83 Approved [3]
Nodal marginal zone lymphoma 2A85.0 Approved [2]
Pain MG30-MG3Z Approved [2]
Plasma cell myeloma 2A83.1 Approved [2]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [2]
Prolymphocytic leukaemia 2A82.1 Approved [2]
Recurrent adult burkitt lymphoma 2A85.6 Approved [2]
Small intestine lymphoma N.A. Approved [2]
Splenic marginal zone lymphoma N.A. Approved [2]
Testicular lymphoma N.A. Approved [2]
Urinary bladder neoplasm N.A. Approved [2]
Waldenstrom macroglobulinemia 2A85.4 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
Colon cancer 2B90.Z Investigative [2]
Lenalidomide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tumor necrosis factor (TNF) TTF8CQI TNFA_HUMAN Inhibitor [9]
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Lenalidomide Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
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Lenalidomide Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Fibroblast growth factor receptor 1 (FGFR1) OT4GLCXW FGFR1_HUMAN Affects Expression [11]
Interleukin-1 receptor type 1 (IL1R1) OTTU8959 IL1R1_HUMAN Decreases Expression [12]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Decreases Expression [12]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) OTDS2EAR TNR1B_HUMAN Decreases Expression [12]
Fibroblast growth factor receptor 2 (FGFR2) OTLOPACK FGFR2_HUMAN Decreases Expression [11]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Decreases Expression [11]
Proteinase-activated receptor 1 (F2R) OT4WVWBO PAR1_HUMAN Decreases Expression [12]
TGF-beta receptor type-1 (TGFBR1) OT40S1SJ TGFR1_HUMAN Decreases Expression [12]
Interleukin-6 receptor subunit beta (IL6ST) OT1N9C70 IL6RB_HUMAN Decreases Expression [12]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Decreases Expression [12]
DNA damage-binding protein 1 (DDB1) OTTR2L3Z DDB1_HUMAN Affects Binding [13]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [14]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [15]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Mercaptopurine
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Approved [5]
Acute lymphocytic leukaemia 2B33.3 Approved [6]
Crohn disease DD70 Phase 4 [7]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [8]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [8]
Mercaptopurine Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MERS-CoV papain-like proteinase (PL-PRO) TTYJOLE R1AB_CVEMC (854-2740) Inhibitor [8]
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) TTL7C8Q IMDH1_HUMAN Inhibitor [18]
SARS-CoV papain-like proteinase (PL-PRO) TTRGHB2 R1AB_CVHSA (819-2740) Inhibitor [8]
Amidophosphoribosyltransferase (PPAT) TTZFTY4 PUR1_HUMAN Breaker [19]
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Mercaptopurine Interacts with 9 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [20]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [21]
Multidrug resistance-associated protein 5 (ABCC5) DTYVM24 MRP5_HUMAN Substrate [22]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [23]
Concentrative nucleoside transporter 2 (SLC28A2) DT82KPY S28A2_HUMAN Substrate [24]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3) DT4YL5R S28A3_HUMAN Substrate [25]
Equilibrative nucleoside transporter 1 (SLC29A1) DTXD1TQ S29A1_HUMAN Substrate [24]
Equilibrative nucleoside transporter 2 (SLC29A2) DTW78DQ S29A2_HUMAN Substrate [24]
Equilibrative nucleobase transporter 1 (SLC43A3) DTGBPR5 S43A3_HUMAN Substrate [26]
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⏷ Show the Full List of 9 DTP(s)
Mercaptopurine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [27]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [27]
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Metabolism [28]
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Mercaptopurine Interacts with 20 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Thiopurine S-methyltransferase (TPMT) OTFOX70W TPMT_HUMAN Affects Response To Substance [29]
Nuclear receptor subfamily 4 group A member 3 (NR4A3) OTPBE9R1 NR4A3_HUMAN Increases ADR [30]
Thiopurine S-methyltransferase (TPMT) OTFOX70W TPMT_HUMAN Decreases Metabolism [31]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [32]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) OTPG0K7E IMDH2_HUMAN Increases Expression [32]
Glutathione peroxidase 2 (GPX2) OTXI2NTI GPX2_HUMAN Increases Expression [32]
Glutathione peroxidase 3 (GPX3) OT6PK94R GPX3_HUMAN Increases Expression [32]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Increases Expression [32]
Glutathione synthetase (GSS) OTVSBEIW GSHB_HUMAN Increases Expression [32]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) OTBPMIMW G3P_HUMAN Affects Localization [33]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [34]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Decreases Phosphorylation [16]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Affects Localization [16]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [16]
Molybdenum cofactor sulfurase (MOCOS) OT0TL3Q5 MOCOS_HUMAN Decreases Oxidation [35]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1) OTC6GISG DQA1_HUMAN Affects Response To Substance [36]
Major vault protein (MVP) OTJGHJRB MVP_HUMAN Decreases Response To Substance [37]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) OTRGGIFP DRB1_HUMAN Affects Response To Substance [36]
Glutathione S-transferase Mu 1 (GSTM1) OTSBF2MO GSTM1_HUMAN Affects Response To Substance [17]
Nucleotide triphosphate diphosphatase NUDT15 (NUDT15) OTX8SZOT NUD15_HUMAN Increases Response To Substance [38]
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⏷ Show the Full List of 20 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Invasive ductal carcinoma DCPB867 HS 578T Investigative [39]
Amelanotic melanoma DCT0CIN M14 Investigative [1]
Melanoma DCBHU29 SK-MEL-2 Investigative [1]
Mixed endometrioid and clear cell carcinoma DCSV8YA IGROV1 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 Lenalidomide FDA Label
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: 7331).
4 Low-dose Lenalidomide for Non-severe COVID-19 Treatment Trial (GETAFE)
5 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: 7226).
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
7 ClinicalTrials.gov (NCT00846703) The GD-2008 ALL Protocol for Childhood Acute Lymphoblastic Leukemia. U.S. National Institutes of Health.
8 Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus. Antiviral Res. 2015 Mar;115:9-16.
9 Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
10 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB00480)
11 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.
12 Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood. 2005 Apr 15;105(8):3286-94. doi: 10.1182/blood-2004-06-2101. Epub 2004 Dec 23.
13 Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nat Struct Mol Biol. 2014 Sep;21(9):803-9. doi: 10.1038/nsmb.2874. Epub 2014 Aug 10.
14 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.
15 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.
16 CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest. 2003 Apr;111(8):1133-45. doi: 10.1172/JCI16432.
17 Pharmacogenetics of outcome in children with acute lymphoblastic leukemia. Blood. 2005 Jun 15;105(12):4752-8. doi: 10.1182/blood-2004-11-4544. Epub 2005 Feb 15.
18 Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67.
19 6-mercaptopurine (6-MP) induces p53-mediated apoptosis of neural progenitor cells in the developing fetal rodent brain. Neurotoxicol Teratol. 2009 Jul-Aug;31(4):198-202.
20 ABC transporters and their role in nucleoside and nucleotide drug resistance. Biochem Pharmacol. 2012 Apr 15;83(8):1073-83.
21 Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia. Blood. 2009 Aug 13;114(7):1383-6.
22 Overexpression of MRP4 (ABCC4) and MRP5 (ABCC5) confer resistance to the nucleoside analogs cytarabine and troxacitabine, but not gemcitabine. Springerplus. 2014 Dec 13;3:732.
23 Organic anion transporter 3 is involved in the brain-to-blood efflux transport of thiopurine nucleobase analogs. J Neurochem. 2004 Aug;90(4):931-41.
24 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA2040)
25 Involvement of the concentrative nucleoside transporter 3 and equilibrative nucleoside transporter 2 in the resistance of T-lymphoblastic cell lines to thiopurines. Biochem Biophys Res Commun. 2006 Apr 28;343(1):208-15.
26 Characterization of 6-Mercaptopurine Transport by the SLC43A3-Encoded Nucleobase Transporter. Mol Pharmacol. 2019 Jun;95(6):584-596.
27 Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy. Curr Drug Metab. 2007 Aug;8(6):554-62.
28 The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse. Leukemia. 2010 Apr;24(4):715-20.
29 Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis. J Gastroenterol. 2003;38(8):740-6. doi: 10.1007/s00535-003-1139-2.
30 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
31 Genetic polymorphisms of drug-metabolising enzymes and drug transporters in the chemotherapeutic treatment of cancer. Clin Pharmacokinet. 2006;45(3):253-85. doi: 10.2165/00003088-200645030-00003.
32 Petit E, Langouet S, Akhdar H, Nicolas-Nicolaz C, Guillouzo A, Morel F. Differential toxic effects of azathioprine, 6-mercaptopurine and 6-thioguanine on human hepatocytes. Toxicol In Vitro. 2008;22(3):632-642. [PMID: 18222062]
33 Glyceraldehyde 3-phosphate dehydrogenase depletion induces cell cycle arrest and resistance to antimetabolites in human carcinoma cell lines. J Pharmacol Exp Ther. 2009 Oct;331(1):77-86. doi: 10.1124/jpet.109.155671. Epub 2009 Jul 23.
34 Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
35 Thiopurine-induced toxicity is associated with dysfunction variant of the human molybdenum cofactor sulfurase gene (xanthinuria type II). Toxicol Appl Pharmacol. 2018 Aug 15;353:102-108. doi: 10.1016/j.taap.2018.06.015. Epub 2018 Jun 20.
36 HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants. Nat Genet. 2014 Oct;46(10):1131-4. doi: 10.1038/ng.3093. Epub 2014 Sep 14.
37 Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. Cancer Lett. 2009 Jun 28;279(1):74-83. doi: 10.1016/j.canlet.2009.01.027. Epub 2009 Feb 18.
38 A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nat Genet. 2014 Sep;46(9):1017-20. doi: 10.1038/ng.3060. Epub 2014 Aug 10.
39 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.