Details of the Drug Combination

General Information of Drug Combination (ID: DC1BPA8)

Drug Combination Name

Vemurafenib Pomalidomide

Indication

Disease Entry	Status	REF
Non-small cell lung carcinoma	Investigative	[1]

Component Drugs

Vemurafenib DM62UG5

Pomalidomide DMTGBAX

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: HOP-92

Zero Interaction Potency (ZIP) Score: 1.07

Bliss Independence Score: 4.88

Loewe Additivity Score: 3.75

LHighest Single Agent (HSA) Score: 2.47

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

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]
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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]
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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]
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Vemurafenib Interacts with 8 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]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases 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	[13]
Melanocyte protein PMEL (PMEL)	OTCDDHHM	PMEL_HUMAN	Increases Expression	[5]
Melanoma antigen recognized by T-cells 1 (MLANA)	OT1N2S2K	MAR1_HUMAN	Increases Expression	[5]
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⏷ Show the Full List of 8 DOT(s)

Indication(s) of Pomalidomide

Disease Entry	ICD 11	Status	REF
Plasma cell myeloma	2A83.1	Approved	[3]
Systemic sclerosis	4A42	Approved	[4]

Pomalidomide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiogenesis/myeloma cell growth (AMCG)	TTDIBYJ	NOUNIPROTAC	Modulator	[14]
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Pomalidomide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[15]
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Pomalidomide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[16]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[17]
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Pomalidomide Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[18]
Erythroid transcription factor (GATA1)	OTX1R7O1	GATA1_HUMAN	Decreases Expression	[18]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Decreases Expression	[18]
Transcription factor PU.1 (SPI1)	OTVCA1D0	SPI1_HUMAN	Increases Expression	[18]
Endothelial transcription factor GATA-2 (GATA2)	OTBP2QQ2	GATA2_HUMAN	Decreases Expression	[18]
DNA-binding protein inhibitor ID-1 (ID1)	OTKGNZN5	ID1_HUMAN	Increases Expression	[18]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Increases Expression	[18]
CCAAT/enhancer-binding protein delta (CEBPD)	OTNBIPMY	CEBPD_HUMAN	Increases Expression	[18]
Krueppel-like factor 1 (KLF1)	OT1FK08U	KLF1_HUMAN	Decreases Expression	[18]
CCAAT/enhancer-binding protein epsilon (CEBPE)	OTKZA25M	CEBPE_HUMAN	Increases Expression	[18]
Transcription factor NF-E2 45 kDa subunit (NFE2)	OTLM94BI	NFE2_HUMAN	Decreases Expression	[18]
Zinc finger protein Gfi-1b (GFI1B)	OTRDW8YO	GFI1B_HUMAN	Decreases Expression	[18]
Zinc finger protein Gfi-1 (GFI1)	OT9HB9H8	GFI1_HUMAN	Increases Expression	[18]
Sal-like protein 4 (SALL4)	OTC08PR5	SALL4_HUMAN	Affects Binding	[19]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Oxidation	[20]
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⏷ Show the Full List of 15 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Carcinoma	DCDBP0B	RXF 393	Investigative	[21]
Carcinoma	DCVCX4I	MCF7	Investigative	[21]
Colon carcinoma	DCZSQYQ	KM12	Investigative	[21]
Invasive ductal carcinoma	DCI4BRB	BT-549	Investigative	[21]
Adenocarcinoma	DCG73CU	DU-145	Investigative	[1]
Adenocarcinoma	DC3XDZ7	OVCAR3	Investigative	[1]
Adenocarcinoma	DCTMQ91	NCIH23	Investigative	[1]
Adenocarcinoma	DCWVDGI	HCT-15	Investigative	[1]
Adenocarcinoma	DCXRMWK	HCT116	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCB3R6H	MOLT-4	Investigative	[1]
Astrocytoma	DC3BOXK	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCIXGNL	CCRF-CEM	Investigative	[1]
Chronic myelogenous leukemia	DCRP6LU	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DCU22AG	786-0	Investigative	[1]
Glioblastoma	DCTD85S	SNB-75	Investigative	[1]
Glioma	DC1YQQI	SF-268	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC8VCNR	OVCAR-4	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCE64Q2	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCE8GQX	OVCAR-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCDWLTZ	NCI\\/ADR-RES	Investigative	[1]
Lung adenocarcinoma	DCX7V7X	EKVX	Investigative	[1]
Lung adenocarcinoma	DCGFLBX	MDA-MB-231	Investigative	[1]
Lung adenocarcinoma	DCNC9XE	NCI-H522	Investigative	[1]
Melanoma	DCSDY3C	SK-MEL-2	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCRMPQF	NCI-H322M	Investigative	[1]
Ovarian serous cystadenocarcinoma	DC4H6K9	SK-OV-3	Investigative	[1]
Renal cell carcinoma	DC2G4KX	SN12C	Investigative	[1]
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⏷ Show the Full List of 27 DrugCom(s)

References

1	CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
2	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5893).
3	Pomalidomide FDA Label
4	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7348).
5	PLX4032 Mediated Melanoma Associated Antigen Potentiation in Patient Derived Primary Melanoma Cells. J Cancer. 2015 Oct 29;6(12):1320-30. doi: 10.7150/jca.11126. eCollection 2015.
6	Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation. EMBO J. 2016 Mar 1;35(5):462-78. doi: 10.15252/embj.201592081. Epub 2015 Dec 14.
7	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
8	Differential effects of the oncogenic BRAF inhibitor PLX4032 (vemurafenib) and its progenitor PLX4720 on ABCB1 function. J Pharm Pharm Sci. 2014;17(1):154-68.
9	Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
10	Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43.
11	Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells. Elife. 2015 Aug 18;4:e04640. doi: 10.7554/eLife.04640.
12	Overcoming melanoma resistance to vemurafenib by targeting CCL2-induced miR-34a, miR-100 and miR-125b. Oncotarget. 2016 Jan 26;7(4):4428-41. doi: 10.18632/oncotarget.6599.
13	Melanoma Expressed-CD70 Is Regulated by RhoA and MAPK Pathways without Affecting Vemurafenib Treatment Activity. PLoS One. 2016 Feb 1;11(2):e0148095. doi: 10.1371/journal.pone.0148095. eCollection 2016.
14	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
15	DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08910)
16	Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78.
17	Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72.
18	Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood. 2005 May 15;105(10):3833-40. doi: 10.1182/blood-2004-03-0828. Epub 2004 Aug 3.
19	Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife. 2018 Aug 1;7:e38430. doi: 10.7554/eLife.38430.
20	Human cytochrome P450 oxidation of 5-hydroxythalidomide and pomalidomide, an amino analogue of thalidomide. Chem Res Toxicol. 2014 Jan 21;27(1):147-56. doi: 10.1021/tx4004215. Epub 2013 Dec 24.
21	CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165