General Information of Drug Combination (ID: DCNZEIH)

Drug Combination Name
MK-2206 FORMONONETIN
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs MK-2206   DMT1OZ6 FORMONONETIN   DM7WFZ8
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: 16.206
Bliss Independence Score: 13.701
Loewe Additivity Score: 6.093
LHighest Single Agent (HSA) Score: 9.135

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 20 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Expression [7]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [5]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Increases Expression [7]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [5]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Expression [5]
Tissue factor (F3) OT3MSU3B TF_HUMAN Increases Expression [8]
Vascular endothelial growth factor receptor 1 (FLT1) OTT0OGYS VGFR1_HUMAN Decreases Expression [5]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [5]
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 [9]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [10]
T-lymphocyte activation antigen CD80 (CD80) OTJBLUQE CD80_HUMAN Decreases Expression [5]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Decreases Expression [5]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [10]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [5]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Decreases Expression [11]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [10]
Interferon regulatory factor 8 (IRF8) OT8YSNI4 IRF8_HUMAN Decreases Expression [5]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [10]
Proline-rich AKT1 substrate 1 (AKT1S1) OT4JHN4Y AKTS1_HUMAN Decreases Phosphorylation [12]
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⏷ Show the Full List of 20 DOT(s)
Indication(s) of FORMONONETIN
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [4]
FORMONONETIN Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
SLC5A2 messenger RNA (SLC5A2 mRNA) TTF8JAT SC5A2_HUMAN Inhibitor [4]
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FORMONONETIN Interacts with 19 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Decreases Activity [14]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Decreases Activity [14]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [15]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Increases Activity [15]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Increases Expression [15]
Erythropoietin (EPO) OTZ90CN4 EPO_HUMAN Increases Expression [16]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Affects Binding [17]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Decreases Expression [18]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [19]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [19]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Increases Expression [18]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Increases Expression [18]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Expression [19]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Expression [19]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Expression [19]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Expression [19]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Expression [16]
Estrogen receptor beta (ESR2) OTXNR2WQ ESR2_HUMAN Affects Binding [20]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Decreases Expression [19]
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⏷ Show the Full List of 19 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Hodgkin lymphoma DC2JXK7 U-HO1 Investigative [1]
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References

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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 Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens. Bioorg Med Chem. 2007 May 15;15(10):3445-9.
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 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.
9 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.
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 -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.
12 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.
13 Differential and special properties of the major human UGT1-encoded gastrointestinal UDP-glucuronosyltransferases enhance potential to control chemical uptake. J Biol Chem. 2004 Jan 9;279(2):1429-41.
14 In vivo prediction of CYP-mediated metabolic interaction potential of formononetin and biochanin A using in vitro human and rat CYP450 inhibition data. Toxicol Lett. 2015 Nov 19;239(1):1-8.
15 Red clover aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) agonists enhance genotoxic estrogen metabolism. Chem Res Toxicol. 2017 Nov 20;30(11):2084-2092.
16 Flavonoids from Radix Astragali induce the expression of erythropoietin in cultured cells: a signaling mediated via the accumulation of hypoxia-inducible factor-1. J Agric Food Chem. 2011 Mar 9;59(5):1697-704. doi: 10.1021/jf104018u. Epub 2011 Feb 10.
17 Estrogenic activity of isoflavonoids from Onobrychis ebenoides. Planta Med. 2006 May;72(6):488-93. doi: 10.1055/s-2005-916261.
18 Targeting Oct2 and P53: Formononetin prevents cisplatin-induced acute kidney injury. Toxicol Appl Pharmacol. 2017 Jul 1;326:15-24. doi: 10.1016/j.taap.2017.04.013. Epub 2017 Apr 13.
19 Formononetin potentiates epirubicin-induced apoptosis via ROS production in HeLa cells in vitro. Chem Biol Interact. 2013 Oct 5;205(3):188-97. doi: 10.1016/j.cbi.2013.07.003. Epub 2013 Jul 16.
20 Relationship between estrogen receptor-binding and estrogenic activities of environmental estrogens and suppression by flavonoids. Biosci Biotechnol Biochem. 2002 Jul;66(7):1479-87. doi: 10.1271/bbb.66.1479.