General Information of Drug Combination (ID: DCXJWF5)

Drug Combination Name
Vemurafenib Uracil mustard
Indication
Disease Entry Status REF
Anaplastic large cell lymphoma Investigative [1]
Component Drugs Vemurafenib   DM62UG5 Uracil mustard   DMHL7OB
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SR
Zero Interaction Potency (ZIP) Score: 5.85
Bliss Independence Score: 9.29
Loewe Additivity Score: 4.61
LHighest Single Agent (HSA) Score: 11.21

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 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]
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⏷ Show the Full List of 19 DOT(s)
Indication(s) of Uracil mustard
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Approved [3]
Chronic myelogenous leukaemia 2A20.0 Approved [4]
Polycythemia vera 2A20.4 Approved [4]
Small lymphocytic lymphoma 2A82.0 Approved [4]
Uracil mustard Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [20]
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Uracil mustard Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1 (ART1) OT7FBG5W NAR1_HUMAN Increases ADR [21]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases ADR [21]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Increases ADR [21]
Poly polymerase 1 (PARP1) OTIESHK4 PARP1_ARATH Increases ADR [21]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases ADR [21]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Breast adenocarcinoma DCTCS7T MDA-MB-468 Investigative [22]
Carcinoma DCMJWFP RXF 393 Investigative [22]
Colon carcinoma DC6G37U KM12 Investigative [22]
Invasive ductal carcinoma DCXXYJ1 T-47D Investigative [22]
Adenocarcinoma DCUH7HV HT29 Investigative [1]
Astrocytoma DC17ZFO SNB-19 Investigative [1]
Clear cell renal cell carcinoma DCDC4JX TK-10 Investigative [1]
Clear cell renal cell carcinoma DC06JX4 A498 Investigative [1]
Clear cell renal cell carcinoma DCR5GOS 786-0 Investigative [1]
Clear cell renal cell carcinoma DCL97SP CAKI-1 Investigative [1]
Lung adenocarcinoma DCZC3GG NCI-H522 Investigative [1]
Malignant melanoma DCKRXJ2 UACC62 Investigative [1]
Malignant melanoma DCE15QU LOX IMVI Investigative [1]
Melanoma DC6YLPD SK-MEL-2 Investigative [1]
Melanoma DCCJA8M UACC-257 Investigative [1]
Melanoma DCA6H18 MALME-3M Investigative [1]
Papillary renal cell carcinoma DCDXBUI ACHN Investigative [1]
Pleural epithelioid mesothelioma DCFBDE9 NCI-H226 Investigative [1]
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⏷ Show the Full List of 18 DrugCom(s)

References

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3 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: 7621).
4 Uracil mustard FDA Label
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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.
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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.
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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 Excision of DNA adducts of nitrogen mustards by bacterial and mammalian 3-methyladenine-DNA glycosylases. Carcinogenesis. 1996 Apr;17(4):643-8.
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22 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.