General Information of Drug Combination (ID: DC6VW52)

Drug Combination Name
MK-2206 Erlotinib
Indication
Disease Entry Status REF
Breast and ovarian cancer syndrome Investigative [1]
Component Drugs MK-2206   DMT1OZ6 Erlotinib   DMCMBHA
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: UWB1289
Zero Interaction Potency (ZIP) Score: 6.39
Bliss Independence Score: 6.11
Loewe Additivity Score: 12.63
LHighest Single Agent (HSA) Score: 14.35

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]
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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 [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]
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⏷ Show the Full List of 20 DOT(s)
Indication(s) of Erlotinib
Disease Entry ICD 11 Status REF
Adrenal gland neoplasm N.A. Approved [4]
Adult hepatocellular carcinoma N.A. Approved [4]
Brain cancer 2A00 Approved [4]
Esophageal disorder N.A. Approved [4]
Lung cancer 2C25.0 Approved [4]
Non-small-cell lung cancer 2C25.Y Approved [5]
Pancreatic adenocarcinoma N.A. Approved [4]
Psoriasis EA90 Approved [4]
Salivary gland squamous cell carcinoma N.A. Approved [4]
Pancreatic cancer 2C10 Phase 3 [5]
Colon cancer 2B90.Z Phase 2 [5]
Ependymoma 2A00.0Y Investigative [4]
Neoplastic meningitis N.A. Investigative [4]
Neuroblastoma 2D11.2 Investigative [4]
Erlotinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [14]
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Erlotinib Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [15]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [16]
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Erlotinib Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [17]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [18]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [18]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [18]
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Erlotinib Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Response [19]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DCJPLDH CAOV3 Investigative [20]
Adenocarcinoma DCJB8MD OVCAR3 Investigative [20]
Adenocarcinoma DCGXAII A427 Investigative [20]
Adenocarcinoma DCOCWP7 NCIH1650 Investigative [20]
Adenocarcinoma DCPMTYR NCIH2122 Investigative [20]
Adenocarcinoma DC4631E NCIH23 Investigative [20]
Adenocarcinoma DCEB0J1 NCIH520 Investigative [20]
Adenocarcinoma DCPM2QW COLO320DM Investigative [20]
Adenocarcinoma DC0983O DLD1 Investigative [20]
Adenocarcinoma DC4IT7X HCT116 Investigative [20]
Adenocarcinoma DCW9RYR HT29 Investigative [20]
Adenocarcinoma DC34EVG SW-620 Investigative [20]
Amelanotic melanoma DC81C28 A2058 Investigative [20]
Ewing sarcoma-peripheral primitive neuroectodermal tumour DCVDI8P ES2 Investigative [20]
Germ cell tumour DC94AAK PA1 Investigative [20]
Large cell lung carcinoma DCJ15YY NCI-H460 Investigative [20]
Malignant melanoma DCXEPOG A375 Investigative [20]
Malignant melanoma DC1JTTT HT144 Investigative [20]
Malignant melanoma DC8ZOOL RPMI7951 Investigative [20]
Malignant melanoma DCIUMOL SKMEL30 Investigative [20]
Malignant melanoma DC1VFU2 UACC62 Investigative [20]
Mesothelioma DCBMMHW MSTO Investigative [20]
Non small cell carcinoma DCQT8AB SKMES1 Investigative [20]
Ovarian endometrioid adenocarcinoma DCXSK54 A2780 Investigative [20]
Ovarian serous cystadenocarcinoma DCEIB1X SK-OV-3 Investigative [20]
Prostate carcinoma DCYJO35 LNCAP Investigative [20]
Prostate carcinoma DCI3FI3 VCAP Investigative [20]
Breast and ovarian cancer syndrome DCIPQGO UWB1289+BRCA1 Investigative [1]
Breast carcinoma DCAO7P7 ZR751 Investigative [1]
Breast carcinoma DC59C9R KPL1 Investigative [1]
Breast carcinoma DCHPRV2 OCUBM Investigative [1]
Carcinoma DCOQAG9 OV90 Investigative [1]
Carcinoma DCUXMSD EFM192B Investigative [1]
Carcinoma DCGFZ9N MDAMB436 Investigative [1]
Colon carcinoma DCCTDIE RKO Investigative [1]
Rectal adenocarcinoma DCVJTJK SW837 Investigative [1]
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⏷ Show the Full List of 36 DrugCom(s)

References

1 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.
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 Erlotinib FDA Label
5 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: 4920).
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 Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
15 Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7.
16 Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv Drug Deliv Rev. 2009 Jan 31;61(1):26-33.
17 In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9.
18 Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706.
19 Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. doi: 10.1056/NEJMoa040938. Epub 2004 Apr 29.
20 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.