General Information of Drug Combination (ID: DCWG8IE)

Drug Combination Name
Vemurafenib Plicamycin
Indication
Disease Entry Status REF
Ovarian serous cystadenocarcinoma Investigative [1]
Component Drugs Vemurafenib   DM62UG5 Plicamycin   DM7C8YV
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: SK-OV-3
Zero Interaction Potency (ZIP) Score: 11.48
Bliss Independence Score: 16.82
Loewe Additivity Score: 16.2
LHighest Single Agent (HSA) Score: 16.2

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 [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 [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 [6]
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 [7]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [7]
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 [6]
Melanoma-associated antigen 1 (MAGEA1) OTXAO193 MAGA1_HUMAN Decreases Expression [6]
Thyroxine 5-deiodinase (DIO3) OTNTITOT IOD3_HUMAN Decreases Expression [16]
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 [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 Plicamycin
Disease Entry ICD 11 Status REF
Hypercalcaemia 5B91.0 Approved [3]
Testicular cancer 2C80 Approved [3]
Solid tumour/cancer 2A00-2F9Z Withdrawn from market [4]
Lung cancer 2C25.0 Investigative [5]
Ovarian cancer 2C73 Investigative [5]
Plicamycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RNA synthesis (hRNA synth) TTX2AYW NOUNIPROTAC Modulator [21]
------------------------------------------------------------------------------------
Plicamycin Interacts with 16 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) OT3K7HY5 DHB2_HUMAN Decreases Expression [22]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [23]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Decreases Expression [23]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Expression [23]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [24]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [24]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Decreases Expression [25]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Decreases Expression [20]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Expression [26]
Tissue factor (F3) OT3MSU3B TF_HUMAN Decreases Expression [27]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Expression [28]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Expression [20]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [29]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Decreases Expression [26]
TNFAIP3-interacting protein 1 (TNIP1) OTRAOTEW TNIP1_HUMAN Decreases Expression [30]
Sphingomyelin phosphodiesterase 3 (SMPD3) OTHQBETH NSMA2_HUMAN Decreases Expression [31]
------------------------------------------------------------------------------------
⏷ Show the Full List of 16 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Carcinoma DC05WSL RXF 393 Investigative [32]
Carcinoma DCWHHQN MCF7 Investigative [32]
Colon adenocarcinoma DCH9FDL COLO 205 Investigative [32]
Colon carcinoma DCF9N8A KM12 Investigative [32]
Invasive ductal carcinoma DCX9W8B BT-549 Investigative [32]
Invasive ductal carcinoma DCNLBE5 HS 578T Investigative [32]
Invasive ductal carcinoma DCZTZ9E T-47D Investigative [32]
Adenocarcinoma DCKNOV8 DU-145 Investigative [1]
Adenocarcinoma DCWDJ7M OVCAR3 Investigative [1]
Adenocarcinoma DCX4V28 NCIH23 Investigative [1]
Adenocarcinoma DC38VHF A549 Investigative [1]
Adenocarcinoma DCNPD62 HT29 Investigative [1]
Adenocarcinoma DCQP8CV HCT116 Investigative [1]
Adenocarcinoma DC75NC1 SW-620 Investigative [1]
Adult acute myeloid leukemia DC4HP4E HL-60(TB) Investigative [1]
Amelanotic melanoma DC9IRHW M14 Investigative [1]
Amelanotic melanoma DCPX94P MDA-MB-435 Investigative [1]
Anaplastic large cell lymphoma DCPOKL4 SR Investigative [1]
Astrocytoma DC6J564 SNB-19 Investigative [1]
Childhood T acute lymphoblastic leukemia DC4QSK0 CCRF-CEM Investigative [1]
Chronic myelogenous leukemia DCXI08Y K-562 Investigative [1]
Clear cell renal cell carcinoma DCYV3QO 786-0 Investigative [1]
Clear cell renal cell carcinoma DCA533J A498 Investigative [1]
Clear cell renal cell carcinoma DCCMNUO TK-10 Investigative [1]
Clear cell renal cell carcinoma DCNYD2H CAKI-1 Investigative [1]
Cutaneous melanoma DCQT4Y1 SK-MEL-5 Investigative [1]
Glioblastoma DCAP0KL SNB-75 Investigative [1]
Glioma DCS7X3S SF-268 Investigative [1]
Glioma DC15OV4 SF-295 Investigative [1]
Glioma DC011S5 SF-539 Investigative [1]
High grade ovarian serous adenocarcinoma DCQ1ZBC OVCAR-8 Investigative [1]
High grade ovarian serous adenocarcinoma DCKFN6S OVCAR-5 Investigative [1]
Large cell lung carcinoma DCCYIUS NCI-H460 Investigative [1]
Lung adenocarcinoma DCSKY2I HOP-62 Investigative [1]
Lung adenocarcinoma DCQ8Z73 EKVX Investigative [1]
Lung adenocarcinoma DCM0TGK MDA-MB-231 Investigative [1]
Lung adenocarcinoma DC9WWA4 NCI-H522 Investigative [1]
Malignant melanoma DCQ0NHB LOX IMVI Investigative [1]
Malignant melanoma DCS9CG3 UACC62 Investigative [1]
Melanoma DCVQHZW MALME-3M Investigative [1]
Melanoma DC82YZ1 UACC-257 Investigative [1]
Melanoma DCOO583 SK-MEL-2 Investigative [1]
Minimally invasive lung adenocarcinoma DCRAZRU NCI-H322M Investigative [1]
Mixed endometrioid and clear cell carcinoma DC1IN24 IGROV1 Investigative [1]
Non-small cell lung carcinoma DCJAPNR HOP-92 Investigative [1]
Papillary renal cell carcinoma DCT1WMY ACHN Investigative [1]
Plasma cell myeloma DCD3D9F RPMI-8226 Investigative [1]
Pleural epithelioid mesothelioma DCSTHBE NCI-H226 Investigative [1]
Prostate carcinoma DCZEDLB PC-3 Investigative [1]
Renal cell carcinoma DCSCYQT UO-31 Investigative [1]
Renal cell carcinoma DCFAJ2B SN12C Investigative [1]
------------------------------------------------------------------------------------
⏷ Show the Full List of 51 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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 8394).
5 The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
6 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.
7 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.
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 The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription. Chem Biol Interact. 2014 Aug 5;219:123-32. doi: 10.1016/j.cbi.2014.05.019. Epub 2014 Jun 4.
21 Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
22 SP1 and SP3 mediate progesterone-dependent induction of the 17beta hydroxysteroid dehydrogenase type 2 gene in human endometrium. Biol Reprod. 2006 Oct;75(4):605-14.
23 Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression. Toxicol Appl Pharmacol. 2014 Oct 1;280(1):138-48.
24 Molecular mechanisms of transactivation and doxorubicin-mediated repression of survivin gene in cancer cells. J Biol Chem. 2007 Jan 26;282(4):2615-25. doi: 10.1074/jbc.M606203200. Epub 2006 Nov 22.
25 Sp1 and Sp3 transcription factors regulate the basal expression of human microsomal epoxide hydrolase (EPHX1) through interaction with the E1b far upstream promoter. Gene. 2014 Feb 15;536(1):135-44. doi: 10.1016/j.gene.2013.11.053. Epub 2013 Dec 4.
26 Mithramycin inhibits human epithelial carcinoma cell proliferation and migration involving downregulation of Eps8 expression. Chem Biol Interact. 2010 Jan 5;183(1):181-6. doi: 10.1016/j.cbi.2009.09.018.
27 Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro. Lung. 2004;182(4):251-64. doi: 10.1007/s00408-004-2507-2.
28 The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep. 2008 Jun;28(3):161-76. doi: 10.1042/BSR20080046.
29 CREB/Sp1-mediated MCL1 expression and NFB-mediated ABCB1 expression modulate the cytotoxicity of daunorubicin in chronic myeloid leukemia cells. Toxicol Appl Pharmacol. 2022 Jan 15;435:115847. doi: 10.1016/j.taap.2021.115847. Epub 2021 Dec 25.
30 Sp sites contribute to basal and inducible expression of the human TNIP1 (TNF-inducible protein 3-interacting protein 1) promoter. Biochem J. 2013 Jun 15;452(3):519-29. doi: 10.1042/BJ20121666.
31 Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin. Biochim Biophys Acta. 2009 Nov-Dec;1789(11-12):681-90. doi: 10.1016/j.bbagrm.2009.08.006. Epub 2009 Aug 19.
32 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.