Details of the Drug Combination

General Information of Drug Combination (ID: DC7QJSS)

• Drug Combination Name: Vinorelbine + MK-2206
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Vinorelbine (DMVXFYE): Small molecular drug
  MK-2206 (DMT1OZ6): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DLD1
  Zero Interaction Potency (ZIP) Score: 10.7
  Bliss Independence Score: 12.26
  Loewe Additivity Score: 1.07
  LHighest Single Agent (HSA) Score: 13.82

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vinorelbine

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Non-small-cell lung cancer	2C25.Y	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]

Vinorelbine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[6]

Vinorelbine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

Vinorelbine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[9]

Vinorelbine Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[10]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Expression	[10]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Activity	[11]
Vitamin K-dependent protein C (PROC)	OTGVH484	PROC_HUMAN	Decreases Expression	[12]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[13]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_HUMAN	Increases Expression	[14]
Splicing factor 45 (RBM17)	OT9ROJCL	SPF45_HUMAN	Decreases Response To Substance	[15]
Equilibrative nucleoside transporter 1 (SLC29A1)	OTLOOZZS	S29A1_HUMAN	Affects Response To Substance	[16]
Nucleophosmin (NPM1)	OTTBYYT0	NPM_HUMAN	Decreases Response To Substance	[17]

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	[19]
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	[20]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[18]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Increases Expression	[20]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[18]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Expression	[18]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[21]
Vascular endothelial growth factor receptor 1 (FLT1)	OTT0OGYS	VGFR1_HUMAN	Decreases Expression	[18]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[18]
Endothelin receptor type B (EDNRB)	OTLLZV3P	EDNRB_HUMAN	Increases Expression	[18]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Affects Response To Substance	[22]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[23]
T-lymphocyte activation antigen CD80 (CD80)	OTJBLUQE	CD80_HUMAN	Decreases Expression	[18]
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Decreases Expression	[18]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[23]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Decreases Expression	[18]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Decreases Expression	[24]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[23]
Interferon regulatory factor 8 (IRF8)	OT8YSNI4	IRF8_HUMAN	Decreases Expression	[18]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Decreases Phosphorylation	[23]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Phosphorylation	[25]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast and ovarian cancer syndrome	DCXFCPB	UWB1289	Investigative	[26]
Breast and ovarian cancer syndrome	DCHHSCV	UWB1289+BRCA1	Investigative	[26]
Breast carcinoma	DCQUH50	KPL1	Investigative	[26]
Breast carcinoma	DC9N7XZ	OCUBM	Investigative	[26]
Carcinoma	DC666OK	EFM192B	Investigative	[26]
Carcinoma	DCLL75N	MDAMB436	Investigative	[26]
Colon carcinoma	DCW93CM	RKO	Investigative	[26]
Rectal adenocarcinoma	DCI8YHU	SW837	Investigative	[26]
Adenocarcinoma	DCFBD6M	NCIH1650	Investigative	[1]
Adenocarcinoma	DCLFX4I	NCIH2122	Investigative	[1]
Adenocarcinoma	DCA6KNQ	NCIH23	Investigative	[1]
Adenocarcinoma	DCRF8H2	COLO320DM	Investigative	[1]
Adenocarcinoma	DCCWDAY	HCT116	Investigative	[1]
Adenocarcinoma	DCVDUL2	HT29	Investigative	[1]
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DCR6E3Q	ES2	Investigative	[1]
Germ cell tumour	DC67KRX	PA1	Investigative	[1]
Large cell lung carcinoma	DCNPEC2	NCI-H460	Investigative	[1]
Malignant melanoma	DCZKEM4	RPMI7951	Investigative	[1]
Malignant melanoma	DC8LJQ4	SKMEL30	Investigative	[1]
Mesothelioma	DCLMBSA	MSTO	Investigative	[1]
Non small cell carcinoma	DCEMPCB	SKMES1	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DCP1USN	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCEFP9S	SK-OV-3	Investigative	[1]
Prostate carcinoma	DC1OFV6	LNCAP	Investigative	[1]

References

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• [2] Vinorelbine FDA Label
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