Details of the Drug Combination

General Information of Drug Combination (ID: DCUU94U)

Drug Combination Name
PF-04691502 Cotellic
Indication
Disease Entry Status REF
Embryonal rhabdomyosarcoma Investigative [1]
Component Drugs PF-04691502   DMS610L 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: 15.322
Bliss Independence Score: 14.651
Loewe Additivity Score: 6.767
LHighest Single Agent (HSA) Score: 8.552

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PF-04691502
Disease Entry ICD 11 Status REF
Endometrial cancer 2C76 Phase 2 [2]
PF-04691502 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Modulator [7]
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Modulator [7]
------------------------------------------------------------------------------------
PF-04691502 Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [6]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [8]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Phosphorylation [6]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [6]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [6]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [8]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [8]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [6]
Proline-rich AKT1 substrate 1 (AKT1S1) OT4JHN4Y AKTS1_HUMAN Decreases Phosphorylation [8]
GTPase KRas (KRAS) OT78QCN8 RASK_HUMAN Affects Response To Substance [8]
Serine/threonine-protein kinase B-raf (BRAF) OT7S81XQ BRAF_HUMAN Affects Response To Substance [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Affects Response To Substance [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Affects Response To Substance [8]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 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 DC8GKV1 Rh36 Investigative [1]
Embryonal rhabdomyosarcoma DC7OIAL RD Investigative [1]
------------------------------------------------------------------------------------

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: 7936).
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 PF-04691502 triggers cell cycle arrest, apoptosis and inhibits the angiogenesis in hepatocellular carcinoma cells. Toxicol Lett. 2013 Jul 4;220(2):150-6. doi: 10.1016/j.toxlet.2013.04.018. Epub 2013 Apr 29.
7 PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activity.Mol Cancer Ther.2011 Nov;10(11):2189-99.
8 Synergistic inhibition of ovarian cancer cell growth by combining selective PI3K/mTOR and RAS/ERK pathway inhibitors. Eur J Cancer. 2013 Dec;49(18):3936-44. doi: 10.1016/j.ejca.2013.08.007. Epub 2013 Sep 3.