Details of the Drug Combination

General Information of Drug Combination (ID: DCVO64L)

• Drug Combination Name: Vemurafenib + Raloxifene
• Indication: Invasive ductal carcinoma; Status: Investigative [1]
• Component Drugs:
  Vemurafenib (DM62UG5): Small molecular drug
  Raloxifene (DMDKF3M): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T-47D
  Zero Interaction Potency (ZIP) Score: 2.42
  Bliss Independence Score: 9.75
  Loewe Additivity Score: 9.18
  LHighest Single Agent (HSA) Score: 9.64

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vemurafenib

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[2]

Vemurafenib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase B-raf (BRAF)	TTWCGQT	BRAF_HUMAN	Modulator	[3]

Vemurafenib Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[7]

Vemurafenib Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]

Vemurafenib Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Microphthalmia-associated transcription factor (MITF)	OT6XJCZH	MITF_HUMAN	Affects Expression	[4]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[9]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Decreases Expression	[10]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[11]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[10]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[5]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[5]
CD70 antigen (CD70)	OTHB2AL1	CD70_HUMAN	Decreases Expression	[12]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[10]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Decreases Expression	[13]
Melanocyte protein PMEL (PMEL)	OTCDDHHM	PMEL_HUMAN	Increases Expression	[4]
Melanoma-associated antigen 1 (MAGEA1)	OTXAO193	MAGA1_HUMAN	Decreases Expression	[4]
Thyroxine 5-deiodinase (DIO3)	OTNTITOT	IOD3_HUMAN	Decreases Expression	[14]
Melanoma antigen recognized by T-cells 1 (MLANA)	OT1N2S2K	MAR1_HUMAN	Increases Expression	[4]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[11]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Affects Response To Substance	[15]
Serine/threonine-protein kinase B-raf (BRAF)	OT7S81XQ	BRAF_HUMAN	Increases Response To Substance	[16]
Heat shock 70 kDa protein 1A (HSPA1A)	OTKGIE76	HS71A_HUMAN	Decreases Response To Substance	[17]
GTPase NRas (NRAS)	OTVQ1DG3	RASN_HUMAN	Affects Response To Substance	[15]

Indication(s) of Raloxifene

Disease Entry	ICD 11	Status	REF
Osteoporosis	FB83.0	Approved	[3]

Raloxifene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[18]

Raloxifene Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[19]

Raloxifene Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[20]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[21]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[22]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast adenocarcinoma	DCNY104	MDA-MB-468	Investigative	[1]
Carcinoma	DCOMO3U	MCF7	Investigative	[1]
Invasive ductal carcinoma	DC8II47	HS 578T	Investigative	[1]
Invasive ductal carcinoma	DCIZAED	BT-549	Investigative	[1]
Adenocarcinoma	DCT21A4	DU-145	Investigative	[23]
Adenocarcinoma	DCMEGOI	OVCAR3	Investigative	[23]
Adenocarcinoma	DCSM29I	A549	Investigative	[23]
Adenocarcinoma	DCU59AE	HCT116	Investigative	[23]
Astrocytoma	DC37E6D	SNB-19	Investigative	[23]
Childhood T acute lymphoblastic leukemia	DCP38FI	CCRF-CEM	Investigative	[23]
Chronic myelogenous leukemia	DCS3DOS	K-562	Investigative	[23]
Glioblastoma	DCRR70K	SNB-75	Investigative	[23]
Glioma	DCO73N6	SF-539	Investigative	[23]
Glioma	DCSVOSO	SF-268	Investigative	[23]
High grade ovarian serous adenocarcinoma	DCOKXJM	OVCAR-8	Investigative	[23]
High grade ovarian serous adenocarcinoma	DCAPZ67	OVCAR-4	Investigative	[23]
High grade ovarian serous adenocarcinoma	DC9RZS7	NCI\\/ADR-RES	Investigative	[23]
Large cell lung carcinoma	DC8FJB0	NCI-H460	Investigative	[23]
Lung adenocarcinoma	DC5ERI8	MDA-MB-231	Investigative	[23]
Lung adenocarcinoma	DCBJ5J9	EKVX	Investigative	[23]
Lung adenocarcinoma	DC683PV	NCI-H522	Investigative	[23]
Malignant melanoma	DCI6IDY	LOX IMVI	Investigative	[23]
Melanoma	DCUSHKP	SK-MEL-2	Investigative	[23]
Melanoma	DC9RYK0	UACC-257	Investigative	[23]
Melanoma	DC6GNXZ	MALME-3M	Investigative	[23]
Minimally invasive lung adenocarcinoma	DCGAX2H	NCI-H322M	Investigative	[23]
Non-small cell lung carcinoma	DC6JHES	HOP-92	Investigative	[23]
Ovarian serous cystadenocarcinoma	DCY95VW	SK-OV-3	Investigative	[23]
Papillary renal cell carcinoma	DC9QB02	ACHN	Investigative	[23]
Plasma cell myeloma	DCEAIH5	RPMI-8226	Investigative	[23]
Pleural epithelioid mesothelioma	DCA7WKK	NCI-H226	Investigative	[23]
Prostate carcinoma	DC9SLJS	PC-3	Investigative	[23]
Renal cell carcinoma	DC1Z0UZ	SN12C	Investigative	[23]

References

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• [17] HSP70 Inhibition Limits FAK-Dependent Invasion and Enhances the Response to Melanoma Treatment with BRAF Inhibitors. Cancer Res. 2016 May 1;76(9):2720-30. doi: 10.1158/0008-5472.CAN-15-2137. Epub 2016 Mar 16.
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