Details of the Drug Combination

General Information of Drug Combination (ID: DCXWFUO)

• Drug Combination Name: Talazoparib + PF-05212384
• Indication: TNBC - Triple-Negative Breast Cancer; Status: Phase 1 [1]
• Component Drugs:
  Talazoparib (DM1KS78): Small molecular drug
  PF-05212384 (DMBL3VD): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

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]

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	[5]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[5]

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	[6]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Affects Expression	[6]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Affects Expression	[6]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Affects Expression	[6]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Affects Expression	[6]
Poly polymerase 2 (PARP2)	OTYL81ZI	PARP2_HUMAN	Decreases Activity	[7]
Breast cancer type 1 susceptibility protein (BRCA1)	OT5BN6VH	BRCA1_HUMAN	Increases Response To Substance	[6]
Fumarate hydratase, mitochondrial (FH)	OTEQWU6Q	FUMH_HUMAN	Increases Response To Substance	[8]
Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB)	OTRE1M1T	SDHB_HUMAN	Increases Response To Substance	[8]

Indication(s) of PF-05212384

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]

PF-05212384 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Modulator	[9]
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Modulator	[9]

References

• [1] ClinicalTrials.gov (NCT03911973) Gedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1/2 Positive, HER2 Negative Breast Cancers
• [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] 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: 7940).
• [5] DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB11760)
• [6] 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.
• [7] 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.
• [8] 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.
• [9] First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95.