Details of the Drug Combination

General Information of Drug Combination (ID: DCRLRHD)

Drug Combination Name
LY2523355 ABT-263
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs LY2523355   DMCV602 ABT-263   DMNE56X
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: TC-71
Zero Interaction Potency (ZIP) Score: 13.293
Bliss Independence Score: 15.649
Loewe Additivity Score: 8.064
LHighest Single Agent (HSA) Score: 11.199

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of LY2523355
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Phase 2 [2]
LY2523355 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Kinesin-like protein KIF11 (KIF11) TTTRP0H KIF11_HUMAN Modulator [6]
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Indication(s) of ABT-263
Disease Entry ICD 11 Status REF
Myelofibrosis 2A20.2 Phase 3 [3]
Relapsed or refractory chronic lymphocytic leukaemia 2A82.0 Phase 2 [4]
Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 2 [5]
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 [7]
G1/S-specific cyclin-D1 (CCND1) TTFCJ7S CCND1_HUMAN Inhibitor [8]
Apoptosis regulator Bcl-2 (BCL-2) TTJGNVC BCL2_HUMAN Inhibitor [7]
Apoptosis regulator Bcl-xL (BCL-xL) TTU1E82 B2CL1_HUMAN Inhibitor [7]
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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 [9]
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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 [10]
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ABT-263 Interacts with 6 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 [11]
Gelsolin (GSN) OT4KS2UU GELS_HUMAN Increases Cleavage [12]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [11]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [12]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [12]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Affects Response To Substance [11]
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⏷ Show the Full List of 6 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 ClinicalTrials.gov (NCT01416389) A Study of LY2523355 in Patients With Breast Cancer. U.S. National Institutes of Health.
3 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.
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: 8319).
5 Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.Nat Rev Drug Discov. 2016 Aug;15(8):533-50.
6 Kinesins and cancer. Nat Rev Cancer. 2012 Jul 24;12(8):527-39.
7 Clinical pipeline report, company report or official report of Roche (2009).
8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9 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.
10 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.
11 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.
12 BCL2/BCL-X(L) inhibition induces apoptosis, disrupts cellular calcium homeostasis, and prevents platelet activation. Blood. 2011 Jun 30;117(26):7145-54. doi: 10.1182/blood-2011-03-344812. Epub 2011 May 11.