Details of the Drug Combination

General Information of Drug Combination (ID: DCJRS9U)

Drug Combination Name
MK-2206 SNX-5422
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs MK-2206   DMT1OZ6 SNX-5422   DMIU0VP
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: 1.125
Bliss Independence Score: 0.824
Loewe Additivity Score: 2.319
LHighest Single Agent (HSA) Score: 3.969

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 [6]
E2 ubiquitin-conjugating enzyme T (UBE2T) TT0A1R8 UBE2T_HUMAN Inhibitor [3]
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MK-2206 Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Increases Expression [7]
Endothelin receptor type B (EDNRB) OTLLZV3P EDNRB_HUMAN Increases Expression [5]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Affects Response To Substance [8]
T-lymphocyte activation antigen CD80 (CD80) OTJBLUQE CD80_HUMAN Decreases Expression [5]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [5]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Decreases Expression [9]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [10]
Interferon regulatory factor 8 (IRF8) OT8YSNI4 IRF8_HUMAN Decreases Expression [5]
Proline-rich AKT1 substrate 1 (AKT1S1) OT4JHN4Y AKTS1_HUMAN Decreases Phosphorylation [11]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of SNX-5422
Disease Entry ICD 11 Status REF
Haematological malignancy 2B33.Y Phase 1/2 [4]
Non-small-cell lung cancer 2C25.Y Phase 1/2 [4]
Chronic lymphocytic leukaemia 2A82.0 Phase 1 [4]
Neuroendocrine cancer 2B72.1 Phase 1 [4]
SNX-5422 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Heat shock protein 90 alpha (HSP90A) TT78R5H HS90A_HUMAN Inhibitor [12]
Heat shock protein 90 beta (HSP90B) TTH5YN2 HS90B_HUMAN Inhibitor [4]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
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 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.
6 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.
7 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.
8 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.
9 -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.
10 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.
11 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.
12 SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hema... Blood. 2009 Jan 22;113(4):846-55.