Details of the Drug Combination

General Information of Drug Combination (ID: DCJ3JYK)

• Drug Combination Name: Talazoparib + Pacritinib
• Indication: Primary Myelofibrosis; Status: Phase 1 [1]
• Component Drugs:
  Talazoparib (DM1KS78): Small molecular drug
  Pacritinib (DM1T6ZN): 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 Pacritinib

Disease Entry	ICD 11	Status	REF
Myelofibrosis	2A20.2	Approved	[4]

Pacritinib Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Janus kinase 2 (JAK-2)	TTRMX3V	JAK2_HUMAN	Modulator	[9]
Fms-like tyrosine kinase 3 (FLT-3)	TTGJCWZ	FLT3_HUMAN	Modulator	[10]

References

• [1] ClinicalTrials.gov (NCT06218628) Pacritinib w/ Talazoparib in Pts w/ Myeloproliferative Neoplasms Unresponsive to JAK2 Inhibition
• [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] FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 208712.
• [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] National Cancer Institute Drug Dictionary (drug id 609888).
• [10] 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. (Target id: 1807).