General Information of Drug Combination (ID: DCZZLC2)

Drug Combination Name
LIAROZOLE Nilotinib
Indication
Disease Entry Status REF
Amelanotic melanoma Investigative [1]
Component Drugs LIAROZOLE   DM4OYXE Nilotinib   DM7HXWT
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: MDA-MB-435
Zero Interaction Potency (ZIP) Score: 0.08
Bliss Independence Score: 2.8
Loewe Additivity Score: 2.6
LHighest Single Agent (HSA) Score: 1.8

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of LIAROZOLE
Disease Entry ICD 11 Status REF
Dermatological disease DA24.Y Phase 2/3 [2]
LIAROZOLE Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [4]
Cytochrome P450 26 (CYP26A1) TTD7Q0R CP26A_HUMAN Inhibitor [5]
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LIAROZOLE Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 26A1 (CYP26A1) OTL1DFWV CP26A_HUMAN Decreases Activity [6]
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Indication(s) of Nilotinib
Disease Entry ICD 11 Status REF
Chronic myelogenous leukaemia 2A20.0 Approved [3]
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 [10]
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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 [11]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [12]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [11]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [13]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [13]
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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 [14]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [15]
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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 [16]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Affects Response To Substance [17]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [18]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [18]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [18]
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Increases Phosphorylation [18]
Retinal dehydrogenase 2 (ALDH1A2) OTJB560Z AL1A2_HUMAN Decreases Expression [8]
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Decreases Phosphorylation [9]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [9]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Secretion [19]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [9]
Homeobox protein Hox-B7 (HOXB7) OTC7WYU8 HXB7_HUMAN Increases Expression [8]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [20]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [20]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [9]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Decreases Phosphorylation [21]
Transcription factor JunB (JUNB) OTG2JXV5 JUNB_HUMAN Increases Expression [9]
Homeobox protein Hox-B9 (HOXB9) OTMVHQOU HXB9_HUMAN Increases Expression [8]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6) OTAFHAVI ATF6A_HUMAN Decreases Expression [9]
Histidine decarboxylase (HDC) OT4WA5YQ DCHS_HUMAN Decreases Expression [22]
Paired box protein Pax-3 (PAX3) OTN5PJZV PAX3_HUMAN Decreases Expression [8]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [23]
Paired box protein Pax-6 (PAX6) OTOC9876 PAX6_HUMAN Increases Expression [8]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [9]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [9]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Increases Expression [9]
Homeobox protein MOX-1 (MEOX1) OTJEMT2D MEOX1_HUMAN Decreases Expression [8]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [20]
Mesoderm posterior protein 2 (MESP2) OT7H4LYA MESP2_HUMAN Decreases Expression [8]
Transcription factor 15 (TCF15) OTA6UCWC TCF15_HUMAN Decreases Expression [8]
Oligodendrocyte transcription factor 3 (OLIG3) OTU8XLAF OLIG3_HUMAN Increases Expression [8]
ER degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1) OTWHN69S EDEM1_HUMAN Increases Expression [9]
Eyes absent homolog 1 (EYA1) OTHU807A EYA1_HUMAN Decreases Expression [8]
Forkhead box protein C2 (FOXC2) OT83P1E0 FOXC2_HUMAN Decreases Expression [8]
Neurogenin-2 (NEUROG2) OTAEMIGT NGN2_HUMAN Increases Expression [8]
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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 DCD5W55 RXF 393 Investigative [24]
Adenocarcinoma DC2MTBG HT29 Investigative [1]
Lung adenocarcinoma DCZIEYL HOP-62 Investigative [1]
Lung adenocarcinoma DCNYBMJ MDA-MB-231 Investigative [1]
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References

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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: 5697).
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14 Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87.
15 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
16 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.
17 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.
18 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.
19 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.
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