Details of the Drug Combination

General Information of Drug Combination (ID: DCJ5RLZ)

• Drug Combination Name: Vemurafenib + Lenalidomide
• Indication: Invasive ductal carcinoma; Status: Investigative [1]
• Component Drugs:
  Vemurafenib (DM62UG5): Small molecular drug
  Lenalidomide (DM6Q7U4): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: BT-549
  Zero Interaction Potency (ZIP) Score: 0.99
  Bliss Independence Score: 8.01
  Loewe Additivity Score: 5.58
  LHighest Single Agent (HSA) Score: 5.8

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	[8]

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	[9]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[10]

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	[11]

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	[6]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[12]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Decreases Expression	[13]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[14]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[13]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[7]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[7]
CD70 antigen (CD70)	OTHB2AL1	CD70_HUMAN	Decreases Expression	[15]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[13]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Decreases Expression	[16]
Melanocyte protein PMEL (PMEL)	OTCDDHHM	PMEL_HUMAN	Increases Expression	[6]
Melanoma-associated antigen 1 (MAGEA1)	OTXAO193	MAGA1_HUMAN	Decreases Expression	[6]
Thyroxine 5-deiodinase (DIO3)	OTNTITOT	IOD3_HUMAN	Decreases Expression	[17]
Melanoma antigen recognized by T-cells 1 (MLANA)	OT1N2S2K	MAR1_HUMAN	Increases Expression	[6]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[14]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Affects Response To Substance	[18]
Serine/threonine-protein kinase B-raf (BRAF)	OT7S81XQ	BRAF_HUMAN	Increases Response To Substance	[19]
Heat shock 70 kDa protein 1A (HSPA1A)	OTKGIE76	HS71A_HUMAN	Decreases Response To Substance	[20]
GTPase NRas (NRAS)	OTVQ1DG3	RASN_HUMAN	Affects Response To Substance	[18]

Indication(s) of Lenalidomide

Disease Entry	ICD 11	Status	REF
Adult T-cell leukemia/lymphoma	N.A.	Approved	[3]
Advanced cancer	2A00-2F9Z	Approved	[3]
Complex regional pain syndrome type 1	N.A.	Approved	[3]
Hepatosplenic T-cell lymphoma	N.A.	Approved	[3]
Large granular lymphocytic leukemia	2A90.1	Approved	[3]
Leukemia	N.A.	Approved	[3]
MALT lymphoma	N.A.	Approved	[3]
Multiple myeloma	2A83	Approved	[4]
Nodal marginal zone lymphoma	2A85.0	Approved	[3]
Pain	MG30-MG3Z	Approved	[3]
Plasma cell myeloma	2A83.1	Approved	[3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[3]
Prolymphocytic leukaemia	2A82.1	Approved	[3]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[3]
Small intestine lymphoma	N.A.	Approved	[3]
Splenic marginal zone lymphoma	N.A.	Approved	[3]
Testicular lymphoma	N.A.	Approved	[3]
Urinary bladder neoplasm	N.A.	Approved	[3]
Waldenstrom macroglobulinemia	2A85.4	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[5]
Colon cancer	2B90.Z	Investigative	[3]

Lenalidomide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor (TNF)	TTF8CQI	TNFA_HUMAN	Inhibitor	[21]

Lenalidomide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[22]

Lenalidomide Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Fibroblast growth factor receptor 1 (FGFR1)	OT4GLCXW	FGFR1_HUMAN	Affects Expression	[23]
Interleukin-1 receptor type 1 (IL1R1)	OTTU8959	IL1R1_HUMAN	Decreases Expression	[24]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Decreases Expression	[24]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B)	OTDS2EAR	TNR1B_HUMAN	Decreases Expression	[24]
Fibroblast growth factor receptor 2 (FGFR2)	OTLOPACK	FGFR2_HUMAN	Decreases Expression	[23]
Fibroblast growth factor receptor 3 (FGFR3)	OTSAXDIL	FGFR3_HUMAN	Decreases Expression	[23]
Proteinase-activated receptor 1 (F2R)	OT4WVWBO	PAR1_HUMAN	Decreases Expression	[24]
TGF-beta receptor type-1 (TGFBR1)	OT40S1SJ	TGFR1_HUMAN	Decreases Expression	[24]
Interleukin-6 receptor subunit beta (IL6ST)	OT1N9C70	IL6RB_HUMAN	Decreases Expression	[24]
Angiopoietin-1 receptor (TEK)	OT78YN57	TIE2_HUMAN	Decreases Expression	[24]
DNA damage-binding protein 1 (DDB1)	OTTR2L3Z	DDB1_HUMAN	Affects Binding	[25]
Sal-like protein 4 (SALL4)	OTC08PR5	SALL4_HUMAN	Affects Binding	[26]
Protein cereblon (CRBN)	OTXH9MDC	CRBN_HUMAN	Increases Response To Substance	[27]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Invasive ductal carcinoma	DCYOFFV	HS 578T	Investigative	[1]
Glioma	DC0R7EY	SF-268	Investigative	[28]
Plasma cell myeloma	DCGD34V	RPMI-8226	Investigative	[28]

References

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• [3] Lenalidomide FDA Label
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• [19] The BRAFT1799A mutation confers sensitivity of thyroid cancer cells to the BRAFV600E inhibitor PLX4032 (RG7204). Biochem Biophys Res Commun. 2011 Jan 28;404(4):958-62. doi: 10.1016/j.bbrc.2010.12.088. Epub 2010 Dec 23.
• [20] 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.
• [21] Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351.
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• [23] Thalidomide and Its Analogs Differentially Target Fibroblast Growth Factor Receptors: Thalidomide Suppresses FGFR Gene Expression while Pomalidomide Dampens FGFR2 Activity. Chem Res Toxicol. 2019 Apr 15;32(4):589-602. doi: 10.1021/acs.chemrestox.8b00286. Epub 2019 Mar 15.
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