Details of the Drug Combination

General Information of Drug Combination (ID: DCBMCCC)

• Drug Combination Name: ABT-263 + FORMONONETIN
• Indication: Ewing sarcoma; Status: Investigative [1]
• Component Drugs:
  ABT-263 (DMNE56X): Small molecular drug
  FORMONONETIN (DM7WFZ8): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-71
  Zero Interaction Potency (ZIP) Score: 11.286
  Bliss Independence Score: 9.747
  Loewe Additivity Score: 2.298
  LHighest Single Agent (HSA) Score: 6.141

Molecular Interaction Atlas of This Drug Combination

Indication(s) of ABT-263

Disease Entry	ICD 11	Status	REF
Myelofibrosis	2A20.2	Phase 3	[2]
Relapsed or refractory chronic lymphocytic leukaemia	2A82.0	Phase 2	[3]
Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[4]

ABT-263 Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Apoptosis regulator Bcl-W (BCL-W)	TTQ79W8	B2CL2_HUMAN	Inhibitor	[6]
G1/S-specific cyclin-D1 (CCND1)	TTFCJ7S	CCND1_HUMAN	Inhibitor	[7]
Apoptosis regulator Bcl-2 (BCL-2)	TTJGNVC	BCL2_HUMAN	Inhibitor	[6]
Apoptosis regulator Bcl-xL (BCL-xL)	TTU1E82	B2CL1_HUMAN	Inhibitor	[6]

ABT-263 Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]

ABT-263 Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]

ABT-263 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[10]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[10]

Indication(s) of FORMONONETIN

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[5]

FORMONONETIN Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
SLC5A2 messenger RNA (SLC5A2 mRNA)	TTF8JAT	SC5A2_HUMAN	Inhibitor	[5]

FORMONONETIN Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[12]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
• [2] ClinicalTrials.gov (NCT04472598) Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis (TRANSFORM-1). U.S. National Institutes of Health.
• [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: 8319).
• [4] Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.Nat Rev Drug Discov. 2016 Aug;15(8):533-50.
• [5] Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens. Bioorg Med Chem. 2007 May 15;15(10):3445-9.
• [6] Clinical pipeline report, company report or official report of Roche (2009).
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] The B-cell lymphoma 2 (BCL2)-inhibitors, ABT-737 and ABT-263, are substrates for P-glycoprotein. Biochem Biophys Res Commun. 2011 May 6;408(2):344-9.
• [9] Effect of rifampin on the pharmacokinetics, safety and tolerability of navitoclax (ABT-263), a dual inhibitor of Bcl-2 and Bcl-XL , in patients with cancer. J Clin Pharm Ther. 2014 Dec;39(6):680-4.
• [10] Human breast cancer cells display different sensitivities to ABT-263 based on the level of survivin. Toxicol In Vitro. 2018 Feb;46:229-236. doi: 10.1016/j.tiv.2017.09.023. Epub 2017 Sep 23.
• [11] Differential and special properties of the major human UGT1-encoded gastrointestinal UDP-glucuronosyltransferases enhance potential to control chemical uptake. J Biol Chem. 2004 Jan 9;279(2):1429-41.
• [12] Formononetin potentiates epirubicin-induced apoptosis via ROS production in HeLa cells in vitro. Chem Biol Interact. 2013 Oct 5;205(3):188-97. doi: 10.1016/j.cbi.2013.07.003. Epub 2013 Jul 16.