Details of the Drug Combination

General Information of Drug Combination (ID: DCXGS5G)

• Drug Combination Name: MK-1775 + MK-2206
• Indication: Malignant melanoma; Status: Investigative [1]
• Component Drugs:
  MK-1775 (DM3WDZ5): Small molecular drug
  MK-2206 (DMT1OZ6): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: A375
  Zero Interaction Potency (ZIP) Score: 7.54
  Bliss Independence Score: 9.13
  Loewe Additivity Score: 0.52
  LHighest Single Agent (HSA) Score: 10.04

Molecular Interaction Atlas of This Drug Combination

Indication(s) of MK-1775

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Phase 2	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

MK-1775 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Wee1-like protein kinase (WEE1)	TTJFOAL	WEE1_HUMAN	Inhibitor	[7]

MK-1775 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Phosphorylation	[6]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Response To Substance	[6]

Indication(s) of MK-2206

Disease Entry	ICD 11	Status	REF
Rectal adenocarcinoma	2B92	Phase 2	[4]
Nasopharyngeal carcinoma	2B6B	Investigative	[5]

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	[5]

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]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCFC43W	CAOV3	Investigative	[1]
Adenocarcinoma	DCCO6X0	A427	Investigative	[1]
Adenocarcinoma	DC7JPOQ	NCIH2122	Investigative	[1]
Adenocarcinoma	DCPF5PE	NCIH23	Investigative	[1]
Adenocarcinoma	DC369HV	NCIH520	Investigative	[1]
Adenocarcinoma	DC52IWZ	COLO320DM	Investigative	[1]
Adenocarcinoma	DCQHCN2	HCT116	Investigative	[1]
Adenocarcinoma	DCQJKT4	HT29	Investigative	[1]
Adenocarcinoma	DCYS0LN	SW-620	Investigative	[1]
Amelanotic melanoma	DCPZ8QH	A2058	Investigative	[1]
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DC3JZJ4	ES2	Investigative	[1]
Germ cell tumour	DC3R8WO	PA1	Investigative	[1]
Large cell lung carcinoma	DCB8UL3	NCI-H460	Investigative	[1]
Malignant melanoma	DCI0AK7	RPMI7951	Investigative	[1]
Malignant melanoma	DCAUF9J	SKMEL30	Investigative	[1]
Malignant melanoma	DCOP21X	UACC62	Investigative	[1]
Non small cell carcinoma	DCK8X1R	SKMES1	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DCDJCT3	A2780	Investigative	[1]
Prostate carcinoma	DC9S7QC	VCAP	Investigative	[1]
Breast and ovarian cancer syndrome	DCHT9J8	UWB1289	Investigative	[16]
Breast carcinoma	DC2MXPD	KPL1	Investigative	[16]
Breast carcinoma	DCCFBFL	OCUBM	Investigative	[16]
Carcinoma	DCIIOM2	MDAMB436	Investigative	[16]
Colon carcinoma	DCQ1TMN	RKO	Investigative	[16]
Invasive ductal carcinoma	DCY9QLV	T-47D	Investigative	[16]
Rectal adenocarcinoma	DCQ8DJH	SW837	Investigative	[16]

References

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• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] 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).
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• [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.
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