Details of the Drug Combination

General Information of Drug Combination (ID: DCAI3T3)

Drug Combination Name
CB-839 Talazoparib
Indication
Disease Entry Status REF
Solid Tumor Phase 1 [1]
Component Drugs CB-839   DM094UH Talazoparib   DM1KS78
N.A. 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 CB-839
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 2 [2]
Renal cell carcinoma 2C90 Phase 2 [2]
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
leukaemia 2A60-2B33 Phase 1 [3]
CB-839 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Glutaminase (GLS) TTCW0KX GLSK_HUMAN; GLSL_HUMAN Modulator [6]
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CB-839 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glutaminase kidney isoform, mitochondrial (GLS) OTGOZG2M GLSK_HUMAN Decreases Activity [7]
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Indication(s) of Talazoparib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [4]
Psoriatic arthritis FA21 Phase 3 [5]
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 [4]
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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 [8]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
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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 [9]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Affects Expression [9]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Affects Expression [9]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Affects Expression [9]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Expression [9]
Poly polymerase 2 (PARP2) OTYL81ZI PARP2_HUMAN Decreases Activity [10]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Increases Response To Substance [9]
Fumarate hydratase, mitochondrial (FH) OTEQWU6Q FUMH_HUMAN Increases Response To Substance [11]
Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB) OTRE1M1T SDHB_HUMAN Increases Response To Substance [11]
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⏷ Show the Full List of 9 DOT(s)

References

1 ClinicalTrials.gov (NCT03875313) Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 ClinicalTrials.gov (NCT02071862) Study of the Glutaminase Inhibitor CB-839 in Solid Tumors. U.S. National Institutes of Health.
4 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
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: 8313).
6 Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther. 2014 Apr;13(4):890-901.
7 Dual inhibition of glutaminase and carnitine palmitoyltransferase decreases growth and migration of glutaminase inhibition-resistant triple-negative breast cancer cells. J Biol Chem. 2019 Jun 14;294(24):9342-9357.
8 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB11760)
9 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.
10 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.
11 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.