General Information of Drug Combination (ID: DC27003)

Drug Combination Name
Taxol MK-2206
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Taxol   DMUOT9V MK-2206   DMT1OZ6
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: COLO320DM
Zero Interaction Potency (ZIP) Score: 9.98
Bliss Independence Score: 10.76
Loewe Additivity Score: 11.14
LHighest Single Agent (HSA) Score: 11.6

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Taxol
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [2]
Solid tumour/cancer 2A00-2F9Z Approved [3]
Pancreatic cancer 2C10 Phase 3 [4]
Gastric adenocarcinoma 2B72 Phase 2 [5]
Ovarian cancer 2C73 Phase 2 [5]
Taxol Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Apoptosis regulator Bcl-2 (BCL-2) TTJGNVC BCL2_HUMAN Modulator [2]
Tubulin beta (TUBB) TTYFKSZ NOUNIPROTAC Modulator [2]
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Indication(s) of MK-2206
Disease Entry ICD 11 Status REF
Rectal adenocarcinoma 2B92 Phase 2 [6]
Nasopharyngeal carcinoma 2B6B Investigative [7]
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 [9]
E2 ubiquitin-conjugating enzyme T (UBE2T) TT0A1R8 UBE2T_HUMAN Inhibitor [7]
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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 [10]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [8]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Increases Expression [10]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [8]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Expression [8]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [11]
Vascular endothelial growth factor receptor 1 (FLT1) OTT0OGYS VGFR1_HUMAN Decreases Expression [8]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [8]
Endothelin receptor type B (EDNRB) OTLLZV3P EDNRB_HUMAN Increases Expression [8]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Affects Response To Substance [12]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [13]
T-lymphocyte activation antigen CD80 (CD80) OTJBLUQE CD80_HUMAN Decreases Expression [8]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Decreases Expression [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [13]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [8]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Decreases Expression [14]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [13]
Interferon regulatory factor 8 (IRF8) OT8YSNI4 IRF8_HUMAN Decreases Expression [8]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [13]
Proline-rich AKT1 substrate 1 (AKT1S1) OT4JHN4Y AKTS1_HUMAN Decreases Phosphorylation [15]
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⏷ Show the Full List of 20 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Breast and ovarian cancer syndrome DCFWXTH UWB1289 Investigative [16]
Breast and ovarian cancer syndrome DCPCV4D UWB1289+BRCA1 Investigative [16]
Breast carcinoma DCB62J1 OCUBM Investigative [16]
Carcinoma DC3R9FT EFM192B Investigative [16]
Carcinoma DCOD2BL MDAMB436 Investigative [16]
Colon carcinoma DC64ZXE RKO Investigative [16]
Adenocarcinoma DC73SRK CAOV3 Investigative [1]
Adenocarcinoma DC1P3ZJ A427 Investigative [1]
Adenocarcinoma DCPRNN5 NCIH1650 Investigative [1]
Adenocarcinoma DCLZISZ NCIH2122 Investigative [1]
Adenocarcinoma DC60SO0 NCIH23 Investigative [1]
Adenocarcinoma DCO9LA1 NCIH520 Investigative [1]
Adenocarcinoma DCH6DQ7 DLD1 Investigative [1]
Adenocarcinoma DC14W6C HCT116 Investigative [1]
Adenocarcinoma DC7L7U5 HT29 Investigative [1]
Adenocarcinoma DCAZM5J SW-620 Investigative [1]
Amelanotic melanoma DCOQ454 A2058 Investigative [1]
Germ cell tumour DCXUPS5 PA1 Investigative [1]
Large cell lung carcinoma DC8CKMN NCI-H460 Investigative [1]
Malignant melanoma DCFZXEW HT144 Investigative [1]
Malignant melanoma DCU3636 RPMI7951 Investigative [1]
Malignant melanoma DC7D1DL SKMEL30 Investigative [1]
Mesothelioma DCO4U0W MSTO Investigative [1]
Non small cell carcinoma DCVF4DG SKMES1 Investigative [1]
Ovarian endometrioid adenocarcinoma DCH2R6J A2780 Investigative [1]
Ovarian serous cystadenocarcinoma DCVXZOM SK-OV-3 Investigative [1]
Prostate carcinoma DCX2VXT VCAP Investigative [1]
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⏷ Show the Full List of 27 DrugCom(s)

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 Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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 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).
7 UBE2T promotes nasopharyngeal carcinoma cell proliferation, invasion, and metastasis by activating the AKT/GSK3/-catenin pathway.Oncotarget. 2016 Mar 22;7(12):15161-72.
8 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.
9 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.
10 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.
11 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.
12 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.
13 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.
14 -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.
15 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.
16 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.