Details of the Drug Combination

General Information of Drug Combination (ID: DC06BXJ)

Drug Combination Name
calindol GSK2126458
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs calindol   DMY9P6E GSK2126458   DMM7ZXR
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 4.866
Bliss Independence Score: 5.884
Loewe Additivity Score: 2.218
LHighest Single Agent (HSA) Score: 6.452

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of calindol
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
calindol Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
G-protein coupled receptor GPCR33 (GPRC6A) TTI1PRE GPC6A_HUMAN Modulator (allosteric modulator) [4]
Extracellular calcium-sensing receptor (CASR) TTBUYHA CASR_HUMAN Modulator (allosteric modulator) [5]
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Indication(s) of GSK2126458
Disease Entry ICD 11 Status REF
Lymphoma 2A80-2A86 Phase 1 [3]
GSK2126458 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Modulator [6]
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GSK2126458 Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Decreases Phosphorylation [7]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [7]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [8]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [8]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [7]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [8]
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⏷ Show the Full List of 7 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 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: 719).
3 Dual PI3K/mTOR inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma. Mol Cancer Ther. 2015 Feb;14(2):429-39.
4 Molecular determinants of non-competitive antagonist binding to the mouse GPRC6A receptor. Cell Calcium. 2009 Nov-Dec;46(5-6):323-32.
5 N2-benzyl-N1-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamines and conformationally restrained indole analogues: development of calindol as a new calcimimetic acting at the calcium sensing receptor.Bioorg Med Chem Lett. 2004 Jun 21;14(12):3345-9.
6 Company report (GSK)
7 Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells. Cancer Biol Ther. 2011 Jun 1;11(11):938-46. doi: 10.4161/cbt.11.11.15527. Epub 2011 Jun 1.
8 Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.