General Information of Drug Combination (ID: DCCFR4Y)

Drug Combination Name
ABIRATERONE Nilotinib
Indication
Disease Entry Status REF
Large cell lung carcinoma Investigative [1]
Component Drugs ABIRATERONE   DM8V75C Nilotinib   DM7HXWT
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: NCI-H460
Zero Interaction Potency (ZIP) Score: 6.8
Bliss Independence Score: 6.69
Loewe Additivity Score: 6.52
LHighest Single Agent (HSA) Score: 4.77

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of ABIRATERONE
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Approved [2]
ABIRATERONE Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Steroid 17-alpha-monooxygenase (S17AH) TTRA5BZ CP17A_HUMAN Modulator [4]
------------------------------------------------------------------------------------
ABIRATERONE Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) OTZKVLVJ CP17A_HUMAN Decreases Activity [5]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [6]
Membrane cofactor protein (CD46) OTQ8NWJD MCP_HUMAN Increases Expression [7]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Decreases Response To Substance [8]
------------------------------------------------------------------------------------
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 [12]
------------------------------------------------------------------------------------
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 [13]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [14]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [13]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [15]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [15]
------------------------------------------------------------------------------------
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 [16]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [17]
------------------------------------------------------------------------------------
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 [18]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Affects Response To Substance [19]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [20]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [20]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [20]
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Increases Phosphorylation [20]
Retinal dehydrogenase 2 (ALDH1A2) OTJB560Z AL1A2_HUMAN Decreases Expression [10]
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Decreases Phosphorylation [11]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [11]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Secretion [21]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [11]
Homeobox protein Hox-B7 (HOXB7) OTC7WYU8 HXB7_HUMAN Increases Expression [10]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [22]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [22]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [11]
Breakpoint cluster region protein (BCR) OTCN76C1 BCR_HUMAN Decreases Phosphorylation [23]
Transcription factor JunB (JUNB) OTG2JXV5 JUNB_HUMAN Increases Expression [11]
Homeobox protein Hox-B9 (HOXB9) OTMVHQOU HXB9_HUMAN Increases Expression [10]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6) OTAFHAVI ATF6A_HUMAN Decreases Expression [11]
Histidine decarboxylase (HDC) OT4WA5YQ DCHS_HUMAN Decreases Expression [24]
Paired box protein Pax-3 (PAX3) OTN5PJZV PAX3_HUMAN Decreases Expression [10]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [25]
Paired box protein Pax-6 (PAX6) OTOC9876 PAX6_HUMAN Increases Expression [10]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [11]
Crk-like protein (CRKL) OTOYSD1R CRKL_HUMAN Decreases Phosphorylation [11]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Increases Expression [11]
Homeobox protein MOX-1 (MEOX1) OTJEMT2D MEOX1_HUMAN Decreases Expression [10]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [22]
Mesoderm posterior protein 2 (MESP2) OT7H4LYA MESP2_HUMAN Decreases Expression [10]
Transcription factor 15 (TCF15) OTA6UCWC TCF15_HUMAN Decreases Expression [10]
Oligodendrocyte transcription factor 3 (OLIG3) OTU8XLAF OLIG3_HUMAN Increases Expression [10]
ER degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1) OTWHN69S EDEM1_HUMAN Increases Expression [11]
Eyes absent homolog 1 (EYA1) OTHU807A EYA1_HUMAN Decreases Expression [10]
Forkhead box protein C2 (FOXC2) OT83P1E0 FOXC2_HUMAN Decreases Expression [10]
Neurogenin-2 (NEUROG2) OTAEMIGT NGN2_HUMAN Increases Expression [10]
------------------------------------------------------------------------------------
⏷ 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
Childhood T acute lymphoblastic leukemia DCD99J7 CCRF-CEM Investigative [26]
Chronic myelogenous leukemia DCI1LKN K-562 Investigative [26]
Clear cell renal cell carcinoma DC80G3J CAKI-1 Investigative [26]
Glioma DCFF4RO SF-268 Investigative [26]
Renal cell carcinoma DCB2Q1K SN12C Investigative [26]
Breast adenocarcinoma DC43POE MDA-MB-468 Investigative [27]
Amelanotic melanoma DCXQPZ3 M14 Investigative [1]
Cutaneous melanoma DC75MJE SK-MEL-28 Investigative [1]
Melanoma DCZB1KN SK-MEL-2 Investigative [1]
Prostate carcinoma DCYOKLV PC-3 Investigative [1]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 DrugCom(s)

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 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: 6745).
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).
4 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
5 A fission yeast-based test system for the determination of IC50 values of anti-prostate tumor drugs acting on CYP21. J Enzyme Inhib Med Chem. 2006 Oct;21(5):547-56.
6 Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
7 Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer. JCI Insight. 2018 Sep 6;3(17):e121497. doi: 10.1172/jci.insight.121497. eCollection 2018 Sep 6.
8 Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res. 2015 Jul 13;43(12):5880-97. doi: 10.1093/nar/gkv262. Epub 2015 Apr 23.
9 Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases. Food Chem Toxicol. 2016 Apr;90:112-22.
10 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.
11 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.
12 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
13 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.
14 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
15 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
16 Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87.
17 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
18 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.
19 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.
20 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.
21 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.
22 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.
23 AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009 Nov 6;16(5):401-12. doi: 10.1016/j.ccr.2009.09.028.
24 The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells. Blood. 2006 Nov 15;108(10):3538-47. doi: 10.1182/blood-2005-12-028456. Epub 2006 Jul 18.
25 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.
26 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.
27 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.