Details of the Drug Combination

General Information of Drug Combination (ID: DCB5K45)

• Drug Combination Name: Vemurafenib + Letrozole
• Indication: Invasive ductal carcinoma; Status: Investigative [1]
• Component Drugs:
  Vemurafenib (DM62UG5): Small molecular drug
  Letrozole (DMH07Y3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: BT-549
  Zero Interaction Potency (ZIP) Score: 3.14
  Bliss Independence Score: 6.51
  Loewe Additivity Score: 5.31
  LHighest Single Agent (HSA) Score: 3.78

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	[7]

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	[8]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[9]

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	[10]

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	[5]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[11]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Decreases Expression	[12]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[13]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[12]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[6]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[6]
CD70 antigen (CD70)	OTHB2AL1	CD70_HUMAN	Decreases Expression	[14]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[12]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Decreases Expression	[15]
Melanocyte protein PMEL (PMEL)	OTCDDHHM	PMEL_HUMAN	Increases Expression	[5]
Melanoma-associated antigen 1 (MAGEA1)	OTXAO193	MAGA1_HUMAN	Decreases Expression	[5]
Thyroxine 5-deiodinase (DIO3)	OTNTITOT	IOD3_HUMAN	Decreases Expression	[16]
Melanoma antigen recognized by T-cells 1 (MLANA)	OT1N2S2K	MAR1_HUMAN	Increases Expression	[5]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[13]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Affects Response To Substance	[17]
Serine/threonine-protein kinase B-raf (BRAF)	OT7S81XQ	BRAF_HUMAN	Increases Response To Substance	[18]
Heat shock 70 kDa protein 1A (HSPA1A)	OTKGIE76	HS71A_HUMAN	Decreases Response To Substance	[19]
GTPase NRas (NRAS)	OTVQ1DG3	RASN_HUMAN	Affects Response To Substance	[17]

Indication(s) of Letrozole

Disease Entry	ICD 11	Status	REF
Estrogen-receptor positive breast cancer	N.A.	Approved	[3]
Hormonally-responsive breast cancer	2C60-2C65	Approved	[4]

Letrozole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[20]

Letrozole Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[21]
Aromatase (CYP19A1)	DEQX145	CP19A_HUMAN	Metabolism	[22]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[23]

Letrozole Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[24]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Oxidation	[25]
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Increases Oxidation	[25]
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[26]
Dickkopf-related protein 1 (DKK1)	OTRDLUSP	DKK1_HUMAN	Increases Expression	[27]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Increases Expression	[28]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[28]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[29]
Leukemia inhibitory factor (LIF)	OTO46S5S	LIF_HUMAN	Increases Expression	[27]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[30]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[31]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[31]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[32]
Leukemia inhibitory factor receptor (LIFR)	OT36W9O5	LIFR_HUMAN	Increases Expression	[27]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[29]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[31]
Lanosterol 14-alpha demethylase (CYP51A1)	OTAYHG9C	CP51A_HUMAN	Decreases Activity	[33]
Fibroblast growth factor 22 (FGF22)	OTVIX6J0	FGF22_HUMAN	Increases Expression	[27]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast adenocarcinoma	DC33Y34	MDA-MB-468	Investigative	[1]
Carcinoma	DCWXLV5	MCF7	Investigative	[1]
Invasive ductal carcinoma	DCKBSC9	HS 578T	Investigative	[1]
Adenocarcinoma	DC6ZOQW	HCT-15	Investigative	[34]
Adenocarcinoma	DC9F4QF	HCT116	Investigative	[34]
Adult acute myeloid leukemia	DC0X2RZ	HL-60(TB)	Investigative	[34]
Astrocytoma	DC75W88	SNB-19	Investigative	[34]
Glioma	DCNA32Y	SF-268	Investigative	[34]
High grade ovarian serous adenocarcinoma	DCIVTHE	OVCAR-4	Investigative	[34]
Lung adenocarcinoma	DCVF3ZJ	EKVX	Investigative	[34]
Minimally invasive lung adenocarcinoma	DCX3Y5O	NCI-H322M	Investigative	[34]
Non-small cell lung carcinoma	DCJ5S5U	HOP-92	Investigative	[34]
Ovarian serous cystadenocarcinoma	DCV2FAF	SK-OV-3	Investigative	[34]
Plasma cell myeloma	DCM40Y4	RPMI-8226	Investigative	[34]
Pleural epithelioid mesothelioma	DC9Z977	NCI-H226	Investigative	[34]
Prostate carcinoma	DC48YAO	PC-3	Investigative	[34]
Renal cell carcinoma	DC7MLZO	SN12C	Investigative	[34]

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