General Information of Drug Combination (ID: DCAZWM4)

Drug Combination Name
ABT-263 Buparlisib
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs ABT-263   DMNE56X Buparlisib   DM1WEHC
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: 21.015
Bliss Independence Score: 26.621
Loewe Additivity Score: 9.253
LHighest Single Agent (HSA) Score: 11.903

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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]
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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 [8]
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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 [9]
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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 [10]
Gelsolin (GSN) OT4KS2UU GELS_HUMAN Increases Cleavage [11]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [10]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [11]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [11]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Affects Response To Substance [10]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Buparlisib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 3 [5]
Buparlisib Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase beta (PIK3CB) TTTHBCA PK3CB_HUMAN Inhibitor [13]
PI3-kinase delta (PIK3CD) TTGBPJE PK3CD_HUMAN Inhibitor [13]
PI3-kinase alpha (PIK3CA) TTEUNMR PK3CA_HUMAN Inhibitor [13]
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Inhibitor [13]
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Buparlisib Interacts with 18 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Telomerase reverse transcriptase (TERT) OT085VVA TERT_HUMAN Decreases Expression [12]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [14]
Forkhead box protein O3 (FOXO3) OTHXQG4P FOXO3_HUMAN Increases Expression [14]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [15]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [12]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Increases Phosphorylation [15]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [15]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [15]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Increases Phosphorylation [15]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [12]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Increases Phosphorylation [15]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [16]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [12]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [12]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Expression [12]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [12]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1) OTAYZMOY SIR1_HUMAN Decreases Expression [12]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Response To Substance [17]
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⏷ Show the Full List of 18 DOT(s)

References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
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 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: 7878).
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 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.
12 Inhibition of PI3K signaling pathway enhances the chemosensitivity of APL cells to ATO: Proposing novel therapeutic potential for BKM120. Eur J Pharmacol. 2018 Dec 15;841:10-18. doi: 10.1016/j.ejphar.2018.10.007. Epub 2018 Oct 11.
13 Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
14 Inhibition of PI3K pathway using BKM120 intensified the chemo-sensitivity of breast cancer cells to arsenic trioxide (ATO). Int J Biochem Cell Biol. 2019 Nov;116:105615. doi: 10.1016/j.biocel.2019.105615. Epub 2019 Sep 17.
15 Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer. Cancer Lett. 2014 Jun 1;347(2):204-11. doi: 10.1016/j.canlet.2014.02.018. Epub 2014 Feb 24.
16 The dual PI3K/mTOR inhibitor NVP-BEZ235 and chloroquine synergize to trigger apoptosis via mitochondrial-lysosomal cross-talk. Int J Cancer. 2013 Jun 1;132(11):2682-93. doi: 10.1002/ijc.27935. Epub 2012 Dec 4.
17 Characterization of the mechanism of action of the pan class I PI3K inhibitor NVP-BKM120 across a broad range of concentrations. Mol Cancer Ther. 2012 Aug;11(8):1747-57. doi: 10.1158/1535-7163.MCT-11-1021. Epub 2012 May 31.