General Information of Drug Combination (ID: DCTX7DZ)

Drug Combination Name
MK-2206 MK-4827
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs MK-2206   DMT1OZ6 MK-4827   DMLYGH4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: NCIH1650
Zero Interaction Potency (ZIP) Score: 3.09
Bliss Independence Score: 5.01
Loewe Additivity Score: 11.36
LHighest Single Agent (HSA) Score: 12.16

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 [7]
E2 ubiquitin-conjugating enzyme T (UBE2T) TT0A1R8 UBE2T_HUMAN Inhibitor [3]
------------------------------------------------------------------------------------
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 [8]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [6]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Increases Expression [8]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [6]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Expression [6]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [9]
Vascular endothelial growth factor receptor 1 (FLT1) OTT0OGYS VGFR1_HUMAN Decreases Expression [6]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [6]
Endothelin receptor type B (EDNRB) OTLLZV3P EDNRB_HUMAN Increases Expression [6]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Affects Response To Substance [10]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [11]
T-lymphocyte activation antigen CD80 (CD80) OTJBLUQE CD80_HUMAN Decreases Expression [6]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Decreases Expression [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [11]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [6]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Decreases Expression [12]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [11]
Interferon regulatory factor 8 (IRF8) OT8YSNI4 IRF8_HUMAN Decreases Expression [6]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [11]
Proline-rich AKT1 substrate 1 (AKT1S1) OT4JHN4Y AKTS1_HUMAN Decreases Phosphorylation [13]
------------------------------------------------------------------------------------
⏷ Show the Full List of 20 DOT(s)
Indication(s) of MK-4827
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 3 [4]
Breast cancer 2C60-2C65 Phase 2 [5]
Ewing sarcoma 2B52 Phase 1 [5]
MK-4827 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Poly [ADP-ribose] polymerase (PARP) TTEBCY8 NOUNIPROTAC Modulator [14]
------------------------------------------------------------------------------------
MK-4827 Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [15]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [16]
Beta-glucuronidase (GUSB) DEP54UE BGLR_HUMAN Metabolism [16]
------------------------------------------------------------------------------------
MK-4827 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [17]
------------------------------------------------------------------------------------

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DCSSUSV CAOV3 Investigative [1]
Adenocarcinoma DC6NTIW OVCAR3 Investigative [1]
Adenocarcinoma DCUOUSC A427 Investigative [1]
Adenocarcinoma DCXZNOK NCIH2122 Investigative [1]
Adenocarcinoma DCRZWRC NCIH23 Investigative [1]
Adenocarcinoma DCFLUKF NCIH520 Investigative [1]
Adenocarcinoma DCQ5930 COLO320DM Investigative [1]
Adenocarcinoma DC56Y63 DLD1 Investigative [1]
Adenocarcinoma DCLRUJV HCT116 Investigative [1]
Adenocarcinoma DC4V7D6 HT29 Investigative [1]
Adenocarcinoma DC6PSOL SW-620 Investigative [1]
Amelanotic melanoma DCLKM9B A2058 Investigative [1]
Ewing sarcoma-peripheral primitive neuroectodermal tumour DCLU5O8 ES2 Investigative [1]
Germ cell tumour DC0E0CB PA1 Investigative [1]
Large cell lung carcinoma DCMJ6NE NCI-H460 Investigative [1]
Malignant melanoma DCVFCWU A375 Investigative [1]
Malignant melanoma DC9IDR0 HT144 Investigative [1]
Malignant melanoma DCB7NCC RPMI7951 Investigative [1]
Malignant melanoma DCSPTQ5 SKMEL30 Investigative [1]
Malignant melanoma DC9FVKQ UACC62 Investigative [1]
Mesothelioma DCGZD4Z MSTO Investigative [1]
Non small cell carcinoma DCJBWKJ SKMES1 Investigative [1]
Ovarian endometrioid adenocarcinoma DC26H0N A2780 Investigative [1]
Ovarian serous cystadenocarcinoma DC41BAX SK-OV-3 Investigative [1]
Prostate carcinoma DC2RD92 LNCAP Investigative [1]
Prostate carcinoma DCN3MHL VCAP Investigative [1]
Breast and ovarian cancer syndrome DCFG80X UWB1289 Investigative [18]
Breast carcinoma DCPS202 KPL1 Investigative [18]
Breast carcinoma DCADZ15 OCUBM Investigative [18]
Carcinoma DCY2WT1 OV90 Investigative [18]
Carcinoma DCEQC76 EFM192B Investigative [18]
Carcinoma DCGHF2G MDAMB436 Investigative [18]
Colon adenocarcinoma DCA6YBG LOVO Investigative [18]
Colon carcinoma DCFLCNU RKO Investigative [18]
Invasive ductal carcinoma DCBWQD3 T-47D Investigative [18]
------------------------------------------------------------------------------------
⏷ Show the Full List of 35 DrugCom(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: 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 ClinicalTrials.gov (NCT03602859) A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST). U.S. National Institutes of Health.
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 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.
7 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.
8 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.
9 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.
10 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.
11 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.
12 -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.
13 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.
14 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
15 Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85.
16 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
17 Autophagy up-regulated by MEK/ERK promotes the repair of DNA damage caused by aflatoxin B1. Toxicol Mech Methods. 2022 Feb;32(2):87-96. doi: 10.1080/15376516.2021.1968985. Epub 2021 Aug 26.
18 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.