General Information of Drug Combination (ID: DCLUT9S)

Drug Combination Name
MK-2206 Cotellic
Indication
Disease Entry Status REF
Embryonal rhabdomyosarcoma Investigative [1]
Component Drugs MK-2206   DMT1OZ6 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: 15.195
Bliss Independence Score: 15.556
Loewe Additivity Score: 5.645
LHighest Single Agent (HSA) Score: 7.42

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-2206
Disease Entry ICD 11 Status REF
Rectal adenocarcinoma 2B92 Phase 2 [2]
Nasopharyngeal carcinoma 2B6B Investigative [3]
MK-2206 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RAC-gamma serine/threonine-protein kinase (AKT3) TTAZ05C AKT3_HUMAN Modulator [8]
E2 ubiquitin-conjugating enzyme T (UBE2T) TT0A1R8 UBE2T_HUMAN Inhibitor [3]
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MK-2206 Interacts with 20 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Expression [9]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [7]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Increases Expression [9]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [7]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Expression [7]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [10]
Vascular endothelial growth factor receptor 1 (FLT1) OTT0OGYS VGFR1_HUMAN Decreases Expression [7]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [7]
Endothelin receptor type B (EDNRB) OTLLZV3P EDNRB_HUMAN Increases Expression [7]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Affects Response To Substance [11]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [12]
T-lymphocyte activation antigen CD80 (CD80) OTJBLUQE CD80_HUMAN Decreases Expression [7]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Decreases Expression [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [12]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [7]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Decreases Expression [13]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [12]
Interferon regulatory factor 8 (IRF8) OT8YSNI4 IRF8_HUMAN Decreases Expression [7]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [12]
Proline-rich AKT1 substrate 1 (AKT1S1) OT4JHN4Y AKTS1_HUMAN Decreases Phosphorylation [14]
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⏷ Show the Full List of 20 DOT(s)
Indication(s) of Cotellic
Disease Entry ICD 11 Status REF
Melanoma 2C30 Phase 3 [4]
Breast cancer 2C60-2C65 Phase 2 [5]
Head and neck cancer 2D42 Phase 1 [5]
Renal cell carcinoma 2C90 Phase 1 [5]
Solid tumour/cancer 2A00-2F9Z Phase 1 [6]
Urothelial carcinoma 2C92.0 Phase 1 [5]

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Embryonal rhabdomyosarcoma DCM9SVR RD Investigative [1]
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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: 7945).
3 UBE2T promotes nasopharyngeal carcinoma cell proliferation, invasion, and metastasis by activating the AKT/GSK3/-catenin pathway.Oncotarget. 2016 Mar 22;7(12):15161-72.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 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.
7 Chemerin promotes the pathogenesis of preeclampsia by activating CMKLR1/p-Akt/CEBP axis and inducing M1 macrophage polarization. Cell Biol Toxicol. 2022 Aug;38(4):611-628. doi: 10.1007/s10565-021-09636-7. Epub 2021 Aug 16.
8 First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors.J Clin Oncol.2011 Dec 10;29(35):4688-95.
9 Platycodin D potentiates proliferation inhibition and apoptosis induction upon AKT inhibition via feedback blockade in non-small cell lung cancer cells. Sci Rep. 2016 Nov 29;6:37997. doi: 10.1038/srep37997.
10 Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
11 PI3K/AKT inhibitors aggravate death receptor-mediated hepatocyte apoptosis and liver injury. Toxicol Appl Pharmacol. 2019 Oct 15;381:114729. doi: 10.1016/j.taap.2019.114729. Epub 2019 Aug 22.
12 Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels. Oncotarget. 2012 Aug;3(8):811-23. doi: 10.18632/oncotarget.579.
13 -Mangostin alleviates liver fibrosis through Sirtuin 3-superoxide-high mobility group box 1 signaling axis. Toxicol Appl Pharmacol. 2019 Jan 15;363:142-153. doi: 10.1016/j.taap.2018.11.011. Epub 2018 Nov 29.
14 Akt activation by Ca(2+)/calmodulin-dependent protein kinase kinase 2 (CaMKK2) in ovarian cancer cells. J Biol Chem. 2017 Aug 25;292(34):14188-14204. doi: 10.1074/jbc.M117.778464. Epub 2017 Jun 20.