General Information of Drug Combination (ID: DCRD7BW)

Drug Combination Name
Buparlisib Cotellic
Indication
Disease Entry Status REF
Embryonal rhabdomyosarcoma Investigative [1]
Component Drugs Buparlisib   DM1WEHC Cotellic   DMF9M57
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: CTR
Zero Interaction Potency (ZIP) Score: 10.293
Bliss Independence Score: 11.344
Loewe Additivity Score: 5.699
LHighest Single Agent (HSA) Score: 7.349

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Buparlisib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 3 [2]
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 [7]
PI3-kinase delta (PIK3CD) TTGBPJE PK3CD_HUMAN Inhibitor [7]
PI3-kinase alpha (PIK3CA) TTEUNMR PK3CA_HUMAN Inhibitor [7]
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Inhibitor [7]
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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 [6]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [8]
Forkhead box protein O3 (FOXO3) OTHXQG4P FOXO3_HUMAN Increases Expression [8]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [9]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [6]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Increases Phosphorylation [9]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [9]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [9]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Increases Phosphorylation [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [6]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Increases Phosphorylation [9]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [10]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [6]
Baculoviral IAP repeat-containing protein 3 (BIRC3) OT3E95KB BIRC3_HUMAN Decreases Expression [6]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Expression [6]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [6]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1) OTAYZMOY SIR1_HUMAN Decreases Expression [6]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Response To Substance [11]
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⏷ Show the Full List of 18 DOT(s)
Indication(s) of Cotellic
Disease Entry ICD 11 Status REF
Melanoma 2C30 Phase 3 [3]
Breast cancer 2C60-2C65 Phase 2 [4]
Head and neck cancer 2D42 Phase 1 [4]
Renal cell carcinoma 2C90 Phase 1 [4]
Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
Urothelial carcinoma 2C92.0 Phase 1 [4]

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Embryonal rhabdomyosarcoma DCJ2V56 Rh36 Investigative [1]
Embryonal rhabdomyosarcoma DC1URIC RD Investigative [1]
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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 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).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 ClinicalTrials.gov (NCT01106599) A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0623 in Patients With Locally Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health.
6 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.
7 Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
8 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.
9 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.
10 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.
11 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.