DGIdb - VEMURAFENIB Drug Record

VEMURAFENIB chembl:CHEMBL1229517 ApprovedAntineoplastic

Alternate Names:

VEMURAFENIB
RO-5185426
PLX4032
RG-7204
RO-51-85426
PLX-4032
ZELBORAF
RG7204
BRAF(V600E) KINASE INHIBITOR RO5185426
PLX 4032
ZELBORAF®
N-[3-[[5-(4-CHLOROPHENYL)-1H-PYRROLO[2,3-B]PYRIDIN-3-YL]CARBONYL]-2,4-DIFLUOROPHENYL]-1-PROPANESULFONAMIDE
drugbank:08881
chembl:CHEMBL1229517
rxcui:1147220
pubchem.compound:42611257
chemidplus:918504-65-1

Drug Info:

FDA Approval	not approved
Drug Class	small molecule
Drug Indications	antineoplastic agent
FDA Approval	Melanoma (with BRAF V600 mutation)
Drug Class	Kinase Inhibitors

(13 More Sources)

Publications:

Dienstmann et al., 2015, Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors., Cancer Discov
Nicolaides et al., 2011, Targeted therapy for BRAFV600E malignant astrocytoma., Clin. Cancer Res.
Hoftijzer et al., 2009, Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma., Eur. J. Endocrinol.
Rad et al., 2013, A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention., Cancer Cell
Maldonado et al., 2003, Determinants of BRAF mutations in primary melanomas., J. Natl. Cancer Inst.
Yang et al., 2012, Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer., Cancer Res.
Villanueva et al., 2010, Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K., Cancer Cell
Tiacci et al., 2011, BRAF mutations in hairy-cell leukemia., N. Engl. J. Med.
Sosman et al., 2012, Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib., N. Engl. J. Med.
Brose et al., 2002, BRAF and RAS mutations in human lung cancer and melanoma., Cancer Res.
Gupta-Abramson et al., 2008, Phase II trial of sorafenib in advanced thyroid cancer., J. Clin. Oncol.
Ho et al., 2013, Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer., N. Engl. J. Med.
Rizzo et al., 2010, Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?, Cancer Treat. Rev.
Lovly et al., 2012, Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials., PLoS ONE
Falchook et al., 2013, BRAF mutant gastrointestinal stromal tumor: first report of regression with BRAF inhibitor dabrafenib (GSK2118436) and whole exomic sequencing for analysis of acquired resistance., Oncotarget
Mao et al., 2013, Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents., Clin. Cancer Res.
Chen et al., 2014, BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis., PLoS ONE
Nakayama et al., 2008, KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer., Br. J. Cancer
Huillard et al., 2012, Cooperative interactions of BRAFV600E kinase and CDKN2A locus deficiency in pediatric malignant astrocytoma as a basis for rational therapy., Proc. Natl. Acad. Sci. U.S.A.
Peeters et al., 2013, Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer., Clin. Cancer Res.
Nagore et al., 2014, Prognostic value of BRAF mutations in localized cutaneous melanoma., J. Am. Acad. Dermatol.
Pratilas et al., 2008, Genetic predictors of MEK dependence in non-small cell lung cancer., Cancer Res.
McArthur et al., 2014, Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study., Lancet Oncol.
Mao et al., 2011, BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis., Mol. Biol. Rep.
De Roock et al., 2009, Clinical biomarkers in oncology: focus on colorectal cancer., Mol Diagn Ther
Haldar et al., 2011, Epidermal growth factor receptor blockers for the treatment of ovarian cancer., Cochrane Database Syst Rev
Penna et al., 2016, Primary cross-resistance to BRAFV600E-, MEK1/2- and PI3K/mTOR-specific inhibitors in BRAF-mutant melanoma cells counteracted by dual pathway blockade., Oncotarget
Corcoran et al., 2012, EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib., Cancer Discov
Xing et al., 2014, BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence., J. Clin. Oncol.
Tejpar et al., 2010, Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery., Oncologist
Faber et al., 2014, mTOR inhibition specifically sensitizes colorectal cancers with KRAS or BRAF mutations to BCL-2/BCL-XL inhibition by suppressing MCL-1., Cancer Discov
Agaimy et al., 2009, V600E BRAF mutations are alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours., J. Clin. Pathol.
De Roock et al., 2010, Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis., Lancet Oncol.
Kloos et al., 2009, Phase II trial of sorafenib in metastatic thyroid cancer., J. Clin. Oncol.
Ponti et al., 2012, Overwhelming response to Dabrafenib in a patient with double BRAF mutation (V600E; V600M) metastatic malignant melanoma., J Hematol Oncol
Paraiso et al., 2012, The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms., Clin. Cancer Res.
Kirkwood et al., 2012, Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma., Clin. Cancer Res.
Cardarella et al., 2013, Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer., Clin. Cancer Res.
Nissan et al., 2014, Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence., Cancer Res.
Greger et al., 2012, Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations., Mol. Cancer Ther.
Flaherty et al., 2012, Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations., N. Engl. J. Med.
Jalili et al., 2012, Dual suppression of the cyclin-dependent kinase inhibitors CDKN2C and CDKN1A in human melanoma., J. Natl. Cancer Inst.
Gandhi et al., 2009, Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines., PLoS ONE
Rudin et al., 2013, Molecular characterization of acquired resistance to the BRAF inhibitor dabrafenib in a patient with BRAF-mutant non-small-cell lung cancer., J Thorac Oncol
Hauschild et al., 2012, Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial., Lancet
Prahallad et al., 2012, Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR., Nature
Boulalas et al., Mutational analysis of the BRAF gene in transitional cell carcinoma of the bladder., Int. J. Biol. Markers
Sarker et al., 2015, First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors., Clin. Cancer Res.
Crescenzi et al., 2014, Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers., Horm. Metab. Res.
Andrulis et al., 2013, Targeting the BRAF V600E mutation in multiple myeloma., Cancer Discov
Rubinstein et al., 2010, Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032., J Transl Med
Kim et al., 2013, Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation., Thyroid
Dienstmann et al., 2011, BRAF as a target for cancer therapy., Anticancer Agents Med Chem
Chapman et al., 2011, Improved survival with vemurafenib in melanoma with BRAF V600E mutation., N. Engl. J. Med.
Tol et al., 2010, Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab., Eur. J. Cancer
Ji et al., 2013, Vemurafenib synergizes with nutlin-3 to deplete survivin and suppresses melanoma viability and tumor growth., Clin. Cancer Res.
Morris et al., 2013, Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors., Cancer Discov
Sen et al., 2012, Kinase-impaired BRAF mutations in lung cancer confer sensitivity to dasatinib., Sci Transl Med
Patel et al., 2013, Clinical responses to selumetinib (AZD6244; ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma., Cancer
He et al., 2014, Prognostic value of the BRAF V600E mutation in papillary thyroid carcinoma., Oncol Lett
Menzies et al., 2014, Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma., Clin. Cancer Res.
Lam et al., 2010, Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer., J. Clin. Oncol.
Di Nicolantonio et al., 2008, Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer., J. Clin. Oncol.
Zecchin et al., 2013, BRAF V600E is a determinant of sensitivity to proteasome inhibitors., Mol. Cancer Ther.
Hayes et al., 2012, Phase II efficacy and pharmacogenomic study of Selumetinib (AZD6244; ARRY-142886) in iodine-131 refractory papillary thyroid carcinoma with or without follicular elements., Clin. Cancer Res.
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
Meckbach et al., 2014, BRAF-V600 mutations have no prognostic impact in stage IV melanoma patients treated with monochemotherapy., PLoS ONE
Ascierto et al., 2013, Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma., J. Clin. Oncol.
De Roock et al., 2011, KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer., Lancet Oncol.
Walczyk et al., 2014, The BRAF(V600E) mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?, Clin. Endocrinol. (Oxf)
Howell et al., 2011, Both BRAF V600E mutation and older age (≥ 65 years) are associated with recurrent papillary thyroid cancer., Ann. Surg. Oncol.
Wan et al., 2004, Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF., Cell
Flaherty et al., 2012, Improved survival with MEK inhibition in BRAF-mutated melanoma., N. Engl. J. Med.
Coffee et al., 2013, Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer., Clin. Cancer Res.
Kurman et al., 2011, Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm., Hum. Pathol.
Falchook et al., 2012, Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial., Lancet Oncol.
Hatzivassiliou et al., 2013, Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers., Nature
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Rowland et al., 2015, Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer., Br. J. Cancer
Flaherty et al., 2010, Inhibition of mutated, activated BRAF in metastatic melanoma., N. Engl. J. Med.
Ohashi et al., 2012, Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1., Proc. Natl. Acad. Sci. U.S.A.
Falchook et al., 2012, Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial., Lancet
Paik et al., 2011, Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations., J. Clin. Oncol.
Naoki et al., 2002, Missense mutations of the BRAF gene in human lung adenocarcinoma., Cancer Res.
Gautschi et al., 2012, A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib., J Thorac Oncol
Davies et al., 2002, Mutations of the BRAF gene in human cancer., Nature
Jordan et al., 2012, Vemurafenib for the treatment of melanoma., Expert Opin Pharmacother
Shi H et al., 2014, Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy., Cancer Discov
Hoogstraat et al., 2015, Detailed imaging and genetic analysis reveal a secondary BRAF(L505H) resistance mutation and extensive intrapatient heterogeneity in metastatic BRAF mutant melanoma patients treated with vemurafenib., Pigment Cell Melanoma Res
Wagenaar et al., 2014, Resistance to vemurafenib resulting from a novel mutation in the BRAFV600E kinase domain., Pigment Cell Melanoma Res
Dahlman et al., 2012, BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors., Cancer Discov
Sahadudheen et al., 2016, Long Term Survival and Continued Complete Response of Vemurafenib in a Metastatic Melanoma Patient with BRAF V600K Mutation., Case Rep Oncol Med
Bahadoran et al., 2013, Major clinical response to a BRAF inhibitor in a patient with a BRAF L597R-mutated melanoma., J. Clin. Oncol.
Hutchinson et al., 2013, BRAF fusions define a distinct molecular subset of melanomas with potential sensitivity to MEK inhibition., Clin. Cancer Res.
Ribas A et al., 2014, Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a phase 1b study., Lancet Oncol
Ascierto PA et al., 2016, Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial., Lancet Oncol
Hyman et al., 2015, Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations., N. Engl. J. Med.
Hainsworth JD et al., 2018, Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study., J Clin Oncol
Silkin SV et al., 2016, Complete Clinical Response of BRAF-Mutated Cholangiocarcinoma to Vemurafenib, Panitumumab, and Irinotecan., J Gastrointest Cancer
Hong et al., 2016, Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation., Cancer Discov
Sharman et al., 2014, Vemurafenib response in 2 patients with posttransplant refractory BRAF V600E-mutated multiple myeloma., Clin Lymphoma Myeloma Leuk
Brose et al., 2016, Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial., Lancet Oncol.
Klempner et al., 2016, BRAFV600E Mutations in High-Grade Colorectal Neuroendocrine Tumors May Predict Responsiveness to BRAF-MEK Combination Therapy., Cancer Discov
Larkin et al., 2014, Combined vemurafenib and cobimetinib in BRAF-mutated melanoma., N. Engl. J. Med.
Ali et al., 2014, Extended Antitumor Response of a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib., Case Rep Oncol
Savarese et al., beta-Adrenergic receptor decrease in diabetic rat hearts., Life Sci.
Whittaker et al., 2013, A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition., Cancer Discov
Dietrich et al., 2012, BRAF inhibition in refractory hairy-cell leukemia., N. Engl. J. Med.
Peng et al., 2015, Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers., Cancer Cell
Yao et al., 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS., Nature
Nazarian et al., 2010, Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation., Nature
Gautschi et al., 2013, Lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib., Lung Cancer
Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov
Peters et al., 2013, Dramatic response induced by vemurafenib in a BRAF V600E-mutated lung adenocarcinoma., J. Clin. Oncol.
Tiacci et al., 2015, Targeting Mutant BRAF in Relapsed or Refractory Hairy-Cell Leukemia., N. Engl. J. Med.
Lin et al., 2015, The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies., Nat. Genet.
Joshi et al., 2015, Trametinib with or without vemurafenib in BRAF mutated non-small cell lung cancer., PLoS ONE
Kotschy et al., 2016, The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models., Nature
Mok et al., 2015, Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition., BMC Cancer
Yao et al., 2015, BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms that Determine Their Sensitivity to Pharmacologic Inhibition., Cancer Cell
Wagle et al., 2011, Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling., J. Clin. Oncol.
Herrero et al., 2015, Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes., Cancer Cell
Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov
Chen et al., 2016, Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120., Cancer Discov
Peh et al., 2016, The Combination of Vemurafenib and Procaspase-3 Activation Is Synergistic in Mutant BRAF Melanomas., Mol. Cancer Ther.
Shen et al., 2016, Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma., Nat. Med.
Karoulia et al., 2016, An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling., Cancer Cell
Zick et al., 2017, Treatment inferred from mutations identified using massive parallel sequencing leads to clinical benefit in some heavily pretreated cancer patients., Medicine (Baltimore)
Kirouac et al., 2017, Clinical responses to ERK inhibition in BRAF(V600E)-mutant colorectal cancer predicted using a computational model., NPJ Syst Biol Appl
Bonnevaux et al., 2016, Concomitant Inhibition of PI3Kβ and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kβ-Selective Inhibitor., Mol. Cancer Ther.
Choi et al., 2014, Identification of PLX4032-resistance mechanisms and implications for novel RAF inhibitors., Pigment Cell Melanoma Res
Kordes et al., 2016, Cooperation of BRAF(F595L) and mutant HRAS in histiocytic sarcoma provides new insights into oncogenic BRAF signaling., Leukemia
Banerjee et al., 2016, A Rare Finding of a BRAF Mutation in Renal Cell Carcinoma with Response to BRAF-Directed Targeted Therapy., Cureus
Narita et al., 2014, Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib-resistant melanoma harboring the MEK1-C121S mutation in a preclinical model., Mol. Cancer Ther.
Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.
Sweetlove et al., 2015, Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth., Front Oncol
Feng et al., 2016, A Novel Plant Sesquiterpene Lactone Derivative, DETD-35, Suppresses BRAFV600E Mutant Melanoma Growth and Overcomes Acquired Vemurafenib Resistance in Mice., Mol. Cancer Ther.
Feng et al., 2015, SBI-0640756 Attenuates the Growth of Clinically Unresponsive Melanomas by Disrupting the eIF4F Translation Initiation Complex., Cancer Res.
Montero-Conde et al., 2013, Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF-mutant thyroid carcinomas., Cancer Discov
Yaeger et al., 2015, Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic colorectal cancer patients., Clin. Cancer Res.
Kopetz et al., 2015, Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer., J. Clin. Oncol.
Connolly et al., 2014, Anticancer activity of combination targeted therapy using cetuximab plus vemurafenib for refractory BRAF (V600E)-mutant metastatic colorectal carcinoma., Curr Oncol
Budina-Kolomets et al., 2016, HSP70 Inhibition Limits FAK-Dependent Invasion and Enhances the Response to Melanoma Treatment with BRAF Inhibitors., Cancer Res.
Yang W et al., 2015, Design, synthesis and biological evaluation of bis-aryl ureas and amides based on 2-amino-3-purinylpyridine scaffold as DFG-out B-Raf kinase inhibitors., Eur J Med Chem
Tsai et al., 2008, Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity., Proc. Natl. Acad. Sci. U.S.A.
Donadieu J et al., 2019, Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study., J Clin Oncol
Ugurel S et al., 2015, A multicenter DeCOG study on predictors of vemurafenib therapy outcome in melanoma: pretreatment impacts survival., Ann Oncol
Selt F et al., 2017, Establishment and application of a novel patient-derived KIAA1549:BRAF-driven pediatric pilocytic astrocytoma model for preclinical drug testing., Oncotarget
Sievert AJ et al., 2013, Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas., Proc Natl Acad Sci U S A
Nikolaev et al., 2011, Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma., Nat. Genet.
Emery et al., 2009, MEK1 mutations confer resistance to MEK and B-RAF inhibition., Proc. Natl. Acad. Sci. U.S.A.
Marks et al., 2008, Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma., Cancer Res.
Bottorff et al., 1995, RAS signalling is abnormal in a c-raf1 MEK1 double mutant., Mol. Cell. Biol.
Trunzer et al., 2013, Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma., J. Clin. Oncol.
Sharma A et al., 2012, Vemurafenib: targeted inhibition of mutated BRAF for treatment of advanced melanoma and its potential in other malignancies., Drugs
Hugo et al., 2015, Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance., Cell
Pietrantonio et al., 2016, MET-Driven Resistance to Dual EGFR and BRAF Blockade May Be Overcome by Switching from EGFR to MET Inhibition in BRAF-Mutated Colorectal Cancer., Cancer Discov
Watson et al., 2014, The RAC1 P29S hotspot mutation in melanoma confers resistance to pharmacological inhibition of RAF., Cancer Res.
Sun et al., 2014, Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma., Nature
Wang et al., 2017, ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition., Cell Rep

VEMURAFENIB STAG3

Interaction Score: 4.26

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
27500726

Sources:
CIViC
VEMURAFENIB PREX2

Interaction Score: 4.26

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24265155

Sources:
CIViC
VEMURAFENIB BRAF

Interaction Score: 3.63

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Clinical Status late trials

Clinical Status early trials

Clinical Status case report

PMIDs:
25656898 22038996 19773371 23845441 14679157 22180495 21156289 21663470 22356324 12460918 18541894 23406027 21129611 22536370 23470635 23251002 24594804 19018267 22586120 23325582 24388723 19010912 24508103 20857202 19537845 21975775 26678033 22448344 25024077 20350999 24163374 19561230 20619739 19255327 23031422 22351686 22048237 23833300 24576830 22389471 23020132 22997239 19238210 23524406 22735384 22281684 19404918 25370471 24570209 23612012 20630094 23489023 21426297 21639808 20413299 23812671 23614898 22649091 22972589 24396464 24583796 20368568 19001320 24107445 22241789 26619011 24586605 23918947 21163703 24354346 21594703 15035987 22663011 23549875 21683865 22805292 23934108 25157968 25989278 20818844 22773810 22608338 21483012 12460919 22743296 12068308 23094782 24265155 25515853 24112705 22798288 26989536 23715574 24345920 25037139 27480103 26287849 29320312 26687137 27729313 24997557 27460442 27048246 25265494 24987354 231718 23288408 22621641 26343583 28783719 21107323 24035431 24265153 23733758 26352686 25665005 25706985 27760111 25939769 26343582 21383288 26267534 24265152 26732095 27297867 27500726 27523909 28514312 28649441 27196754 24283590 26582644 26918217 24448821 27312529 26137449 27048951 26603897 23365119 25589621 26460303 24523613 26984758 25462267 18287029 31513482 25524477 28002790 23533272

Sources:
TALC DTC ClearityFoundationBiomarkers MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions DoCM COSMIC CIViC MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB
VEMURAFENIB CIC

Interaction Score: 1.42

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
28178529

Sources:
CIViC
VEMURAFENIB ATXN1L

Interaction Score: 1.42

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
28178529

Sources:
CIViC
VEMURAFENIB SOX10

Interaction Score: 1.07

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24670642

Sources:
CIViC
VEMURAFENIB RAC1

Interaction Score: 0.8

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
25056119 24265153

Sources:
CIViC
VEMURAFENIB NF1

Interaction Score: 0.8

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23288408 231718

Sources:
CIViC
VEMURAFENIB STAG2

Interaction Score: 0.8

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type decreased response

Approval Status Preclinical - Cell line xenograft

PMIDs:
27500726

Sources:
JAX-CKB CIViC
VEMURAFENIB MAP2K1

Interaction Score: 0.6

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status case report

Pathway activation

Variant Effect gain-of-function

PMIDs:
22197931 19915144 25157968 18632602 7651428 23569304 21383288 22389471 24448821 24265153 27312529

Sources:
JAX-CKB DoCM CIViC
VEMURAFENIB NRAS

Interaction Score: 0.45

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical - Cell culture

PMIDs:
21107323 24265153 22389471 26267534 26343583 27523909 23569304

Sources:
JAX-CKB CIViC PharmGKB
VEMURAFENIB CDKN2A

Interaction Score: 0.2

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24265155

Sources:
CIViC
VEMURAFENIB AKT3

Interaction Score: 0.19

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24265155

Sources:
CIViC
VEMURAFENIB PTEN

Interaction Score: 0.15

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy DETD-35 + Vemurafenib

Approval Status Preclinical - Cell line xenograft

combination therapy SAR260301 + Vemurafenib

PMIDs:
24265155 27048951 27196754 24265153 24265152

Sources:
JAX-CKB CIViC
VEMURAFENIB PIK3R2

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24265155

Sources:
CIViC
VEMURAFENIB MAP2K2

Interaction Score: 0.11

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24265153

Sources:
CIViC
VEMURAFENIB PIK3CA

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Selumetinib + Vemurafenib

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
22180495 24265153 26137449 24265155

Sources:
JAX-CKB CIViC
VEMURAFENIB CSF1R

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy PLX3397 + Vemurafenib

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
25939769

Sources:
JAX-CKB
VEMURAFENIB AKT1

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy MK2206 + Vemurafenib

Evidence Type Actionable

PMIDs:
24265152

Sources:
JAX-CKB CIViC
VEMURAFENIB MITF

Interaction Score: 0.08

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24265153

Sources:
CIViC
VEMURAFENIB HRAS

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
VEMURAFENIB MET

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
26359985 27325282

Sources:
CIViC
VEMURAFENIB KRAS

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type resistant

PMIDs:
27312529

Sources:
JAX-CKB PharmGKB
VEMURAFENIB EGFR

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Vemurafenib + Gefitinib

combination therapy Vemurafenib + Panitumumab

Response Type sensitive

PMIDs:
27312529

Sources:
JAX-CKB
VEMURAFENIB ABCB1

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23116250

Sources:
PharmGKB
VEMURAFENIB TP53

Interaction Score: 0.02

Interaction Types & Directionality:

n/a

Interaction Info:

Approval Status Clinical Study

Indication/Tumor Type colon cancer

combination therapy Vemurafenib + Panitumumab

PMIDs:
28514312 26343583

Sources:
JAX-CKB
VEMURAFENIB YES1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
VEMURAFENIB CYP1A2

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23116250

Sources:
PharmGKB
VEMURAFENIB CYP3A4

Interaction Score: 0.0

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23116250

Sources:
PharmGKB

MyCancerGenome: VEMURAFENIB
- Version: 20-Jun-2017
Alternate Names:

PLX-4032 Development Name

RG7204 Development Name

R05185426 Development Name

Drug Info:

Drug Class Kinase Inhibitors

FDA Approval Melanoma (with BRAF V600 mutation)

Publications:
TdgClinicalTrial: VEMURAFENIB
- Version: January-2014
Alternate Names:

Drug Info:

Drug Indications antineoplastic agent

Drug Class small molecule

FDA Approval not approved

Publications:
DTC: VEMURAFENIB
- Version: 02-September-2020
Alternate Names:

CHEMBL1229517 ChEMBL Drug ID

Drug Info:

Publications:

Yang W et al., 2015, Design, synthesis and biological evaluation of bis-aryl ureas and amides based on 2-amino-3-purinylpyridine scaffold as DFG-out B-Raf kinase inhibitors., Eur J Med Chem
PharmGKB: vemurafenib
- Version: 18-August-2020
Alternate Names:

Drug Info:

Publications:

Sharma A et al., 2012, Vemurafenib: targeted inhibition of mutated BRAF for treatment of advanced melanoma and its potential in other malignancies., Drugs

JAX-CKB: Vemurafenib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.

Shi et al., 2014, A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Cancer Discov

Peng et al., 2015, Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers., Cancer Cell

DoCM: VEMURAFENIB

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Flaherty et al., 2012, Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations., N. Engl. J. Med.

Falchook et al., 2012, Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial., Lancet

Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.

CIViC: VEMURAFENIB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Shi H et al., 2014, Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy., Cancer Discov

Ribas A et al., 2014, Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a phase 1b study., Lancet Oncol

Ali et al., 2014, Extended Antitumor Response of a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib., Case Rep Oncol

TTD: Vemurafenib
- Version: 2020.06.01
Alternate Names:

D0Y9EW TTD Drug ID

Drug Info:

Publications:
TALC: VEMURAFENIB
- Version: 12-May-2016
Alternate Names:

VEMURAFENIB Primary Drug Name

VEMURAFENIB Drug Generic Name

ZELBORAF Drug Trade Name

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL1229517
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
ClearityFoundationClinicalTrial: VEMURAFENIB
- Version: 15-June-2013
Alternate Names:

Drug Info:

Publications:
ClearityFoundationBiomarkers: VEMURAFENIB
- Version: 26-July-2013
Alternate Names:

Drug Info:

Publications:
MyCancerGenomeClinicalTrial: VEMURAFENIB
- Version: 30-February-2014
Alternate Names:

Drug Info:

Publications:
OncoKB: Vemurafenib
- Version: 23-July-2020
Alternate Names:

Drug Info:

Publications:
ChemblInteractions: CHEMBL1229517
- Version: chembl_23
Alternate Names:

Drug Info:

Publications:
FDA: Vemurafenib
- Version: 04-September-2020
Alternate Names:

Drug Info:

Publications:
COSMIC: Vemurafenib
- Version: 4-Sep-2020
Alternate Names:

Drug Info:

Publications:

Clinical Status	late trials
Clinical Status	early trials
Clinical Status	case report

Indication/Tumor Type	melanoma
Response Type	decreased response
Approval Status	Preclinical - Cell line xenograft

Clinical Status	case report
Pathway	activation
Variant Effect	gain-of-function

combination therapy	DETD-35 + Vemurafenib
Approval Status	Preclinical - Cell line xenograft
combination therapy	SAR260301 + Vemurafenib

combination therapy	Selumetinib + Vemurafenib
Indication/Tumor Type	melanoma
Response Type	sensitive

combination therapy	PLX3397 + Vemurafenib
Indication/Tumor Type	melanoma
Response Type	sensitive

Evidence Type	Actionable
Approval Status	Preclinical - Cell culture
Response Type	resistant

combination therapy	Vemurafenib + Gefitinib
combination therapy	Vemurafenib + Panitumumab
Response Type	sensitive

Approval Status	Clinical Study
Indication/Tumor Type	colon cancer
combination therapy	Vemurafenib + Panitumumab

PLX-4032	Development Name
RG7204	Development Name
R05185426	Development Name

VEMURAFENIB	Primary Drug Name
VEMURAFENIB	Drug Generic Name
ZELBORAF	Drug Trade Name

VEMURAFENIB Drug Record

VEMURAFENIB chembl:CHEMBL1229517 ApprovedAntineoplastic

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 27500726

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24265155

Sources: CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Clinical Status late trials Clinical Status early trials Clinical Status case report

Sources: TALC DTC ClearityFoundationBiomarkers MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions DoCM COSMIC CIViC MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 28178529

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 28178529

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24670642

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 25056119 24265153

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 23288408 231718

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type melanoma Response Type decreased response Approval Status Preclinical - Cell line xenograft

PMIDs: 27500726

Sources: JAX-CKB CIViC

Interaction Types & Directionality: n/a

Interaction Info: Clinical Status case report Pathway activation Variant Effect gain-of-function

PMIDs: 22197931 19915144 25157968 18632602 7651428 23569304 21383288 22389471 24448821 24265153 27312529

Sources: JAX-CKB DoCM CIViC

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type melanoma Response Type resistant Approval Status Preclinical - Cell culture

PMIDs: 21107323 24265153 22389471 26267534 26343583 27523909 23569304

Sources: JAX-CKB CIViC PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24265155

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24265155

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: combination therapy DETD-35 + Vemurafenib Approval Status Preclinical - Cell line xenograft combination therapy SAR260301 + Vemurafenib

PMIDs: 24265155 27048951 27196754 24265153 24265152

Sources: JAX-CKB CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24265155

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24265153

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Selumetinib + Vemurafenib Indication/Tumor Type melanoma Response Type sensitive

PMIDs: 22180495 24265153 26137449 24265155

Sources: JAX-CKB CIViC

Interaction Types & Directionality: n/a

Interaction Info: combination therapy PLX3397 + Vemurafenib Indication/Tumor Type melanoma Response Type sensitive

PMIDs: 25939769

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Response Type sensitive combination therapy MK2206 + Vemurafenib Evidence Type Actionable

PMIDs: 24265152

Sources: JAX-CKB CIViC

Interaction Types & Directionality:

n/a

PMIDs:
27500726

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
24265155

Sources:
CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Clinical Status late trials

Clinical Status early trials

Clinical Status case report

Sources:
TALC DTC ClearityFoundationBiomarkers MyCancerGenome TdgClinicalTrial ClearityFoundationClinicalTrial JAX-CKB ChemblInteractions DoCM COSMIC CIViC MyCancerGenomeClinicalTrial PharmGKB TTD FDA OncoKB

Interaction Types & Directionality:

n/a

PMIDs:
28178529

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
28178529

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
24670642

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
25056119 24265153

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
23288408 231718

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type decreased response

Approval Status Preclinical - Cell line xenograft

PMIDs:
27500726

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Clinical Status case report

Pathway activation

Variant Effect gain-of-function

PMIDs:
22197931 19915144 25157968 18632602 7651428 23569304 21383288 22389471 24448821 24265153 27312529

Sources:
JAX-CKB DoCM CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type melanoma

Response Type resistant

Approval Status Preclinical - Cell culture

PMIDs:
21107323 24265153 22389471 26267534 26343583 27523909 23569304

Sources:
JAX-CKB CIViC PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
24265155

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
24265155

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy DETD-35 + Vemurafenib

Approval Status Preclinical - Cell line xenograft

combination therapy SAR260301 + Vemurafenib

PMIDs:
24265155 27048951 27196754 24265153 24265152

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

n/a

PMIDs:
24265155

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
24265153

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Selumetinib + Vemurafenib

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
22180495 24265153 26137449 24265155

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy PLX3397 + Vemurafenib

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
25939769

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Response Type sensitive

combination therapy MK2206 + Vemurafenib

Evidence Type Actionable

PMIDs:
24265152

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

n/a

PMIDs:
24265153

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
26359985 27325282

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical - Cell culture

Response Type resistant

PMIDs:
27312529

Sources:
JAX-CKB PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Vemurafenib + Gefitinib

combination therapy Vemurafenib + Panitumumab

Response Type sensitive

PMIDs:
27312529