Details of the Drug Combination

General Information of Drug Combination (ID: DC9UWAB)

• Drug Combination Name: Vismodegib + Epirubicin
• Indication: Breast adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Vismodegib (DM5IXKQ): Small molecular drug
  Epirubicin (DMPDW6T): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: MDA-MB-468
  Zero Interaction Potency (ZIP) Score: 11.07
  Bliss Independence Score: 13.05
  Loewe Additivity Score: 12.66
  LHighest Single Agent (HSA) Score: 13.96

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vismodegib

Disease Entry	ICD 11	Status	REF
Basal cell carcinoma	2C32	Approved	[2]
Primitive neuroectodermal tumour medulloblastoma	2A00.11	Phase 2	[3]

Vismodegib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Smoothened homolog (SMO)	TT8J1S3	SMO_HUMAN	Modulator	[5]

Vismodegib Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[6]

Vismodegib Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Increases Expression	[7]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[7]
Zinc finger protein GLI1 (GLI1)	OT1BTAJO	GLI1_HUMAN	Decreases Expression	[7]
Zinc finger protein GLI2 (GLI2)	OTIRV97L	GLI2_HUMAN	Decreases Expression	[7]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[7]
Platelet-derived growth factor receptor alpha (PDGFRA)	OTDJXUCN	PGFRA_HUMAN	Decreases Expression	[7]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[7]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[7]
Protein patched homolog 1 (PTCH1)	OTMG07H5	PTC1_HUMAN	Decreases Expression	[7]
Protein smoothened (SMO)	OTXXE208	SMO_HUMAN	Decreases Expression	[7]
Protein patched homolog 2 (PTCH2)	OTOQ0K9V	PTC2_HUMAN	Decreases Expression	[7]
Suppressor of fused homolog (SUFU)	OT0IRYG1	SUFU_HUMAN	Decreases Response To Substance	[8]
N-myc proto-oncogene protein (MYCN)	OTWD33K1	MYCN_HUMAN	Decreases Response To Substance	[8]

Indication(s) of Epirubicin

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Approved	[4]

Epirubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[9]

Epirubicin Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[10]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[11]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[11]

Epirubicin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[12]

Epirubicin Interacts with 30 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Expression	[13]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Increases Expression	[13]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[13]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Response To Substance	[14]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Increases Expression	[15]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[16]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[17]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[18]
Retinoic acid receptor alpha (RARA)	OT192V9V	RARA_HUMAN	Affects Mutagenesis	[19]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[13]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Increases Phosphorylation	[20]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[20]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[20]
Protein PML (PML)	OT6SM2GD	PML_HUMAN	Affects Mutagenesis	[19]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[21]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[16]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[16]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Increases Phosphorylation	[20]
FK506-binding protein-like (FKBPL)	OTR9ND6K	FKBPL_HUMAN	Increases Expression	[21]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Increases ADR	[22]
MARVEL domain-containing protein 1 (MARVELD1)	OT5CPOJE	MALD1_HUMAN	Increases Response To Substance	[23]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP)	OT9AGAIJ	LHPP_HUMAN	Increases ADR	[22]
Alpha-protein kinase 1 (ALPK1)	OTBW6SGD	ALPK1_HUMAN	Increases ADR	[24]
Baculoviral IAP repeat-containing protein 6 (BIRC6)	OTCQJAB0	BIRC6_HUMAN	Decreases Response To Substance	[25]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[26]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Affects Response To Substance	[27]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Response To Substance	[28]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Increases Response To Substance	[29]
Little elongation complex subunit 1 (ICE1)	OTOXTBUH	ICE1_HUMAN	Increases ADR	[22]
Microcephalin (MCPH1)	OTYT3TT5	MCPH1_HUMAN	Increases ADR	[24]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Carcinoma	DCX7ZQE	RXF 393	Investigative	[1]
Carcinoma	DCP61QW	MCF7	Investigative	[1]
Colon adenocarcinoma	DCOPWL3	COLO 205	Investigative	[1]
Invasive ductal carcinoma	DCYJXEP	HS 578T	Investigative	[1]
Invasive ductal carcinoma	DC598EZ	BT-549	Investigative	[1]
Invasive ductal carcinoma	DCNGIQQ	T-47D	Investigative	[1]
Adenocarcinoma	DCFRAKY	DU-145	Investigative	[30]
Adenocarcinoma	DCK8UGB	NCIH23	Investigative	[30]
Adenocarcinoma	DCBQVDZ	A549	Investigative	[30]
Adenocarcinoma	DCNEOAT	HCT-15	Investigative	[30]
Adenocarcinoma	DCA1NCN	HT29	Investigative	[30]
Adult T acute lymphoblastic leukemia	DC7ZX63	MOLT-4	Investigative	[30]
Amelanotic melanoma	DCF6SP6	MDA-MB-435	Investigative	[30]
Amelanotic melanoma	DCR06DQ	M14	Investigative	[30]
Astrocytoma	DCH9GNK	U251	Investigative	[30]
Astrocytoma	DCM43HH	SNB-19	Investigative	[30]
Childhood T acute lymphoblastic leukemia	DCQ41NK	CCRF-CEM	Investigative	[30]
Chronic myelogenous leukemia	DCN8098	K-562	Investigative	[30]
Clear cell renal cell carcinoma	DCWXLR7	TK-10	Investigative	[30]
Clear cell renal cell carcinoma	DCNXPY4	A498	Investigative	[30]
Clear cell renal cell carcinoma	DCKH2YP	CAKI-1	Investigative	[30]
Cutaneous melanoma	DCUF09T	SK-MEL-5	Investigative	[30]
Cutaneous melanoma	DC5G1HL	SK-MEL-28	Investigative	[30]
Glioblastoma	DCV4U5M	SNB-75	Investigative	[30]
Glioma	DCSGM2H	SF-539	Investigative	[30]
Glioma	DCJVC08	SF-268	Investigative	[30]
High grade ovarian serous adenocarcinoma	DCEPA15	OVCAR-5	Investigative	[30]
High grade ovarian serous adenocarcinoma	DCZZ5D3	OVCAR-8	Investigative	[30]
High grade ovarian serous adenocarcinoma	DC8LIFS	NCI\\/ADR-RES	Investigative	[30]
Large cell lung carcinoma	DCI07LH	NCI-H460	Investigative	[30]
Lung adenocarcinoma	DCYM41D	MDA-MB-231	Investigative	[30]
Lung adenocarcinoma	DCMTKNG	EKVX	Investigative	[30]
Lung adenocarcinoma	DCLQ3SG	HOP-62	Investigative	[30]
Lung adenocarcinoma	DC5YKLH	NCI-H522	Investigative	[30]
Malignant melanoma	DCW4OB8	LOX IMVI	Investigative	[30]
Melanoma	DCY5Y54	SK-MEL-2	Investigative	[30]
Melanoma	DCTXDAR	UACC-257	Investigative	[30]
Non-small cell lung carcinoma	DCW97TN	HOP-92	Investigative	[30]
Ovarian serous cystadenocarcinoma	DCZB598	SK-OV-3	Investigative	[30]
Papillary renal cell carcinoma	DCPM68T	ACHN	Investigative	[30]
Plasma cell myeloma	DCBVMLB	RPMI-8226	Investigative	[30]
Pleural epithelioid mesothelioma	DCAFIHJ	NCI-H226	Investigative	[30]

References

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• [30] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.