General Information of Drug Combination (ID: DCSSX18)

Drug Combination Name
Lenalidomide Nilotinib
Indication
Disease Entry Status REF
Colon adenocarcinoma Investigative [1]
Component Drugs Lenalidomide   DM6Q7U4 Nilotinib   DM7HXWT
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: COLO 205
Zero Interaction Potency (ZIP) Score: 4.59
Bliss Independence Score: 7.95
Loewe Additivity Score: 3.75
LHighest Single Agent (HSA) Score: 3.51

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 [6]
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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 [7]
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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 [8]
Interleukin-1 receptor type 1 (IL1R1) OTTU8959 IL1R1_HUMAN Decreases Expression [9]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Decreases Expression [9]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) OTDS2EAR TNR1B_HUMAN Decreases Expression [9]
Fibroblast growth factor receptor 2 (FGFR2) OTLOPACK FGFR2_HUMAN Decreases Expression [8]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Decreases Expression [8]
Proteinase-activated receptor 1 (F2R) OT4WVWBO PAR1_HUMAN Decreases Expression [9]
TGF-beta receptor type-1 (TGFBR1) OT40S1SJ TGFR1_HUMAN Decreases Expression [9]
Interleukin-6 receptor subunit beta (IL6ST) OT1N9C70 IL6RB_HUMAN Decreases Expression [9]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Decreases Expression [9]
DNA damage-binding protein 1 (DDB1) OTTR2L3Z DDB1_HUMAN Affects Binding [10]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [11]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [12]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Nilotinib
Disease Entry ICD 11 Status REF
Chronic myelogenous leukaemia 2A20.0 Approved [5]
Nilotinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Fusion protein Bcr-Abl (Bcr-Abl) TTS7G69 BCR_HUMAN-ABL1_HUMAN Modulator [16]
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Nilotinib Interacts with 5 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [17]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [18]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [17]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [19]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [19]
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Nilotinib Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [20]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [21]
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Nilotinib Interacts with 35 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Response To Substance [22]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Affects Response To Substance [23]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [24]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [24]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [24]
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Increases Phosphorylation [24]
Retinal dehydrogenase 2 (ALDH1A2) OTJB560Z AL1A2_HUMAN Decreases Expression [14]
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Decreases Phosphorylation [15]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [15]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Secretion [25]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [15]
Homeobox protein Hox-B7 (HOXB7) OTC7WYU8 HXB7_HUMAN Increases Expression [14]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [26]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [26]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [15]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Decreases Phosphorylation [27]
Transcription factor JunB (JUNB) OTG2JXV5 JUNB_HUMAN Increases Expression [15]
Homeobox protein Hox-B9 (HOXB9) OTMVHQOU HXB9_HUMAN Increases Expression [14]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6) OTAFHAVI ATF6A_HUMAN Decreases Expression [15]
Histidine decarboxylase (HDC) OT4WA5YQ DCHS_HUMAN Decreases Expression [28]
Paired box protein Pax-3 (PAX3) OTN5PJZV PAX3_HUMAN Decreases Expression [14]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [29]
Paired box protein Pax-6 (PAX6) OTOC9876 PAX6_HUMAN Increases Expression [14]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [15]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [15]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Increases Expression [15]
Homeobox protein MOX-1 (MEOX1) OTJEMT2D MEOX1_HUMAN Decreases Expression [14]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [26]
Mesoderm posterior protein 2 (MESP2) OT7H4LYA MESP2_HUMAN Decreases Expression [14]
Transcription factor 15 (TCF15) OTA6UCWC TCF15_HUMAN Decreases Expression [14]
Oligodendrocyte transcription factor 3 (OLIG3) OTU8XLAF OLIG3_HUMAN Increases Expression [14]
ER degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1) OTWHN69S EDEM1_HUMAN Increases Expression [15]
Eyes absent homolog 1 (EYA1) OTHU807A EYA1_HUMAN Decreases Expression [14]
Forkhead box protein C2 (FOXC2) OT83P1E0 FOXC2_HUMAN Decreases Expression [14]
Neurogenin-2 (NEUROG2) OTAEMIGT NGN2_HUMAN Increases Expression [14]
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⏷ Show the Full List of 35 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Carcinoma DCM2FO4 RXF 393 Investigative [1]
Amelanotic melanoma DCGJOU7 MDA-MB-435 Investigative [30]
Melanoma DCAWVV0 MALME-3M Investigative [30]
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References

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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: 5697).
6 Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
7 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB00480)
8 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.
9 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.
10 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.
11 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.
12 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.
13 Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases. Food Chem Toxicol. 2016 Apr;90:112-22.
14 Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
15 Endoplasmic reticulum stress-mediated apoptosis in imatinib-resistant leukemic K562-r cells triggered by AMN107 combined with arsenic trioxide. Exp Biol Med (Maywood). 2013 Aug 1;238(8):932-42. doi: 10.1177/1535370213492689. Epub 2013 Jul 24.
16 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
17 Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties. Br J Pharmacol. 2009 Oct;158(4):1153-64.
18 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
19 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
20 Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87.
21 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
22 Resistance to daunorubicin, imatinib, or nilotinib depends on expression levels of ABCB1 and ABCG2 in human leukemia cells. Chem Biol Interact. 2014 Aug 5;219:203-10. doi: 10.1016/j.cbi.2014.06.009. Epub 2014 Jun 19.
23 Reversal of ABCB1 mediated efflux by imatinib and nilotinib in cells expressing various transporter levels. Chem Biol Interact. 2017 Aug 1;273:171-179. doi: 10.1016/j.cbi.2017.06.012. Epub 2017 Jun 13.
24 Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes. Toxicol Appl Pharmacol. 2013 Oct 1;272(1):245-55.
25 p53 Gene (NY-CO-13) Levels in Patients with Chronic Myeloid Leukemia: The Role of Imatinib and Nilotinib. Diseases. 2018 Jan 25;6(1):13. doi: 10.3390/diseases6010013.
26 Nilotinib reduced the viability of human ovarian cancer cells via mitochondria-dependent apoptosis, independent of JNK activation. Toxicol In Vitro. 2016 Mar;31:1-11. doi: 10.1016/j.tiv.2015.11.002. Epub 2015 Nov 6.
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29 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
30 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.