Details of the Drug Combination

General Information of Drug Combination (ID: DCNKPA6)

Drug Combination Name
Talazoparib ARRY-162
Indication
Disease Entry Status REF
Pancreatic Cancer Phase 1 [1]
Component Drugs Talazoparib   DM1KS78 ARRY-162   DM1P6FR
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Talazoparib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [2]
Psoriatic arthritis FA21 Phase 3 [3]
Talazoparib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Poly [ADP-ribose] polymerase (PARP) TTEBCY8 NOUNIPROTAC Inhibitor [2]
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Talazoparib Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [4]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [4]
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Talazoparib Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Affects Expression [5]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Affects Expression [5]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Affects Expression [5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Affects Expression [5]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Expression [5]
Poly polymerase 2 (PARP2) OTYL81ZI PARP2_HUMAN Decreases Activity [6]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Increases Response To Substance [5]
Fumarate hydratase, mitochondrial (FH) OTEQWU6Q FUMH_HUMAN Increases Response To Substance [7]
Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB) OTRE1M1T SDHB_HUMAN Increases Response To Substance [7]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of ARRY-162
Disease Entry ICD 11 Status REF
Melanoma 2C30 Approved [2]
ARRY-162 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MAPK/ERK kinase kinase (MAP3K) TTROQ37 NOUNIPROTAC Modulator [8]
ERK activator kinase (MEK) TTZCRP3 NOUNIPROTAC Inhibitor [2]
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ARRY-162 Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
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ARRY-162 Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [10]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [11]
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References

1 ClinicalTrials.gov (NCT03637491) A Study of Avelumab, Binimetinib and Talazoparib in Patients With Locally Advanced or Metastatic RAS-mutant Solid Tumors
2 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
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: 8313).
4 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB11760)
5 BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23.
6 Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors. J Med Chem. 2017 Feb 23;60(4):1262-1271. doi: 10.1021/acs.jmedchem.6b00990. Epub 2016 Dec 21.
7 Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair. Nat Genet. 2018 Aug;50(8):1086-1092. doi: 10.1038/s41588-018-0170-4. Epub 2018 Jul 16.
8 MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 2013; 6: 27.
9 The impact of P-glycoprotein and breast cancer resistance protein on the brain pharmacokinetics and pharmacodynamics of a panel of MEK inhibitors. Int J Cancer. 2018 Jan 15;142(2):381-391.
10 FDA Label of Binimetinib. The 2020 official website of the U.S. Food and Drug Administration.
11 Binimetinib - European Medicines Agency - European Union