General Information of Drug Combination (ID: DCX7V7X)

Drug Combination Name
Vemurafenib Pomalidomide
Indication
Disease Entry Status REF
Lung adenocarcinoma Investigative [1]
Component Drugs Vemurafenib   DM62UG5 Pomalidomide   DMTGBAX
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: EKVX
Zero Interaction Potency (ZIP) Score: 3.12
Bliss Independence Score: 5.79
Loewe Additivity Score: 4.51
LHighest Single Agent (HSA) Score: 2.83

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]
------------------------------------------------------------------------------------
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]
------------------------------------------------------------------------------------
⏷ Show the Full List of 19 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 [20]
------------------------------------------------------------------------------------
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 [21]
------------------------------------------------------------------------------------
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 [22]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [23]
------------------------------------------------------------------------------------
Pomalidomide Interacts with 27 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Oxidation [24]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Decreases Secretion [25]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Secretion [25]
Granulocyte colony-stimulating factor (CSF3) OT9GC6TP CSF3_HUMAN Increases Secretion [25]
Fibroblast growth factor receptor 1 (FGFR1) OT4GLCXW FGFR1_HUMAN Decreases Expression [26]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [25]
Erythroid transcription factor (GATA1) OTX1R7O1 GATA1_HUMAN Decreases Expression [25]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Decreases Expression [25]
Transcription factor PU.1 (SPI1) OTVCA1D0 SPI1_HUMAN Increases Expression [25]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [25]
Fibroblast growth factor receptor 3 (FGFR3) OTSAXDIL FGFR3_HUMAN Affects Expression [26]
Endothelial transcription factor GATA-2 (GATA2) OTBP2QQ2 GATA2_HUMAN Decreases Expression [25]
Rhombotin-2 (LMO2) OTCC370G RBTN2_HUMAN Decreases Expression [25]
Interleukin-13 (IL13) OTI4YS3Y IL13_HUMAN Decreases Secretion [25]
DNA-binding protein inhibitor ID-1 (ID1) OTKGNZN5 ID1_HUMAN Increases Expression [25]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Increases Expression [25]
CCAAT/enhancer-binding protein delta (CEBPD) OTNBIPMY CEBPD_HUMAN Increases Expression [25]
DNA-binding protein inhibitor ID-2 (ID2) OT0U1D53 ID2_HUMAN Increases Expression [25]
Krueppel-like factor 1 (KLF1) OT1FK08U KLF1_HUMAN Decreases Expression [25]
CCAAT/enhancer-binding protein epsilon (CEBPE) OTKZA25M CEBPE_HUMAN Increases Expression [25]
Transcription factor NF-E2 45 kDa subunit (NFE2) OTLM94BI NFE2_HUMAN Decreases Expression [25]
Zinc finger protein Gfi-1b (GFI1B) OTRDW8YO GFI1B_HUMAN Decreases Expression [25]
Zinc finger protein Gfi-1 (GFI1) OT9HB9H8 GFI1_HUMAN Increases Expression [25]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Affects Binding [27]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Oxidation [24]
Cytochrome P450 2J2 (CYP2J2) OTJBTEH8 CP2J2_HUMAN Increases Oxidation [24]
Protein cereblon (CRBN) OTXH9MDC CRBN_HUMAN Increases Response To Substance [28]
------------------------------------------------------------------------------------
⏷ Show the Full List of 27 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Carcinoma DCDBP0B RXF 393 Investigative [29]
Carcinoma DCVCX4I MCF7 Investigative [29]
Colon carcinoma DCZSQYQ KM12 Investigative [29]
Invasive ductal carcinoma DCI4BRB BT-549 Investigative [29]
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 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]
Non-small cell lung carcinoma DC1BPA8 HOP-92 Investigative [1]
Ovarian serous cystadenocarcinoma DC4H6K9 SK-OV-3 Investigative [1]
Renal cell carcinoma DC2G4KX SN12C Investigative [1]
------------------------------------------------------------------------------------
⏷ Show the Full List of 27 DrugCom(s)

References

1 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.
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 Role of the protein kinase BRAF in the pathogenesis of endometriosis. Expert Opin Ther Targets. 2016 Aug;20(8):1017-29. doi: 10.1080/14728222.2016.1180367. Epub 2016 May 4.
13 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.
14 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.
15 Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy. Nat Commun. 2018 Jun 27;9(1):2500. doi: 10.1038/s41467-018-04664-0.
16 MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma. Endocr Relat Cancer. 2016 Mar;23(3):135-46. doi: 10.1530/ERC-15-0162.
17 Paradoxical activation of MEK/ERK signaling induced by B-Raf inhibition enhances DR5 expression and DR5 activation-induced apoptosis in Ras-mutant cancer cells. Sci Rep. 2016 May 25;6:26803. doi: 10.1038/srep26803.
18 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.
19 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.
20 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
21 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08910)
22 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.
23 Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72.
24 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.
25 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.
26 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.
27 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.
28 A Dual Color Immunohistochemistry Assay for Measurement of Cereblon in Multiple Myeloma Patient Samples. Appl Immunohistochem Mol Morphol. 2016 Nov/Dec;24(10):695-702. doi: 10.1097/PAI.0000000000000246.
29 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.