DGIdb - DABRAFENIB Drug Record

DABRAFENIB chembl:CHEMBL2028663 ApprovedAntineoplastic

Alternate Names:

GSK2118436A
DABRAFENIB
TAFINLAR
GSK-2118436A
GSK-2118436
GSK2118436
TAFINLAR®
DRB436
rxcui:1424911
pubchem.compound:44462760
drugbank:08912
chemidplus:1195765-45-7
chembl:CHEMBL2028663

Drug Info:

Pharmaceutical Developer	GlaxoSmithKline
Source Reported Drug Name(s)	Dabrafenib/GSK2118436
Drug Class	RAF Inhibitor
FDA Approval	Melanoma (with BRAF V600 mutation)
Drug Class	Kinase Inhibitors
FDA Approval	not approved
Drug Class	Small molecule
Drug Indications	antineoplastic agent
Drug Categories	proto-oncogene proteins b-raf, antagonists & inhibitors
Drug Categories	protein kinase inhibitors
Drug Groups	investigational
Drug Categories	breast cancer resistance protein inhibitors
Drug Categories	cytochrome p-450 cyp2b6 inducers
Drug Categories	cytochrome p-450 cyp2b6 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp2c19 inducers
Drug Categories	cytochrome p-450 cyp2c8 inducers
Drug Categories	cytochrome p-450 cyp2c8 inducers (weak)
Drug Categories	cytochrome p-450 cyp2c8 inhibitors
Drug Categories	cytochrome p-450 cyp2c8 inhibitors (strong)
Drug Categories	cytochrome p-450 cyp2c8 substrates with a narrow therapeutic index
Drug Categories	cytochrome p-450 cyp2c9 inducers
Drug Categories	cytochrome p-450 cyp2c9 inducers (strong)
Drug Categories	cytochrome p-450 cyp3a substrates
Drug Categories	cytochrome p-450 cyp3a4 inducers
Drug Categories	cytochrome p-450 cyp3a4 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp3a4 substrates with a narrow therapeutic index
Drug Categories	cytochrome p-450 enzyme inducers
Drug Categories	cytochrome p-450 enzyme inhibitors
Drug Categories	cytochrome p-450 substrates
Drug Categories	drugs causing inadvertant photosensitivity
Drug Categories	kinase inhibitor
Drug Categories	oat1/slc22a6 inhibitors
Drug Categories	oat3/slc22a8 inhibitors
Drug Categories	oatp1b1/slco1b1 inhibitors
Drug Categories	oatp1b3 inhibitors
Drug Categories	organic anion transporter 1 inhibitors
Drug Categories	organic anion transporting polypeptide 1b1 inhibitors
Drug Categories	organic anion transporting polypeptide 1b3 inhibitors
Drug Categories	p-glycoprotein substrates
Drug Categories	p-glycoprotein substrates with narrow therapeutic index
Drug Categories	photosensitizing agents
Drug Categories	potential qtc-prolonging agents
Drug Categories	qtc prolonging agents

(13 More Sources)

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.
Paik et al., 2011, Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations., J. Clin. Oncol.
Shi H et al., 2014, Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy., Cancer Discov
Paraiso et al., 2012, The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms., Clin. Cancer Res.
Subbiah V et al., 2018, Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic 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.
Horn et al., 2016, High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells., 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
Carlino et al., 2015, Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic melanoma patients., Clin. Cancer Res.
Lam et al., 2010, Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer., J. Clin. Oncol.
Gibson et al., 2017, Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer., Clin. Cancer Res.
Kloos et al., 2009, Phase II trial of sorafenib in metastatic thyroid cancer., J. Clin. Oncol.
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.
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.
Pratilas et al., 2008, Genetic predictors of MEK dependence in non-small cell lung cancer., Cancer Res.
Coffee et al., 2013, Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer., Clin. Cancer Res.
Xing et al., 2014, BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence., J. Clin. Oncol.
Kim et al., 2013, Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation., Thyroid
Casadevall et al., 2016, Dabrafenib in an elderly patient with metastatic melanoma and BRAF V600R mutation: a case report., J Med Case Rep
Gupta-Abramson et al., 2008, Phase II trial of sorafenib in advanced thyroid cancer., J. Clin. Oncol.
Meckbach et al., 2014, BRAF-V600 mutations have no prognostic impact in stage IV melanoma patients treated with monochemotherapy., PLoS ONE
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.
Schreuer et al., 2017, Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAF(V600)-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial., Lancet Oncol.
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.
Bland et al., 1976, Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial., Am. J. Obstet. Gynecol.
Cardarella et al., 2013, Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer., Clin. Cancer Res.
Ji et al., 2013, Vemurafenib synergizes with nutlin-3 to deplete survivin and suppresses melanoma viability and tumor growth., Clin. Cancer Res.
Robert et al., 2015, Improved overall survival in melanoma with combined dabrafenib and trametinib., N. Engl. J. Med.
Nissan et al., 2014, Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence., Cancer Res.
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
Flaherty et al., 2010, Inhibition of mutated, activated BRAF in metastatic melanoma., N. Engl. J. Med.
Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov
Ponti et al., 2013, The somatic affairs of BRAF: tailored therapies for advanced malignant melanoma and orphan non-V600E (V600R-M) mutations., J. Clin. Pathol.
Andrulis et al., 2013, Targeting the BRAF V600E mutation in multiple myeloma., Cancer Discov
Ahronian et al., 2015, Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations., Cancer Discov
Lu et al., 2017, Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer., Cancer Res.
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.
Long GV et al., 2014, Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma., Nat Commun
Sosman et al., 2012, Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib., N. Engl. J. Med.
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.
Lovly et al., 2012, Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials., PLoS ONE
Jalili et al., 2012, Dual suppression of the cyclin-dependent kinase inhibitors CDKN2C and CDKN1A in human melanoma., J. Natl. Cancer Inst.
De Roock et al., 2011, KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer., Lancet Oncol.
Wan et al., 2004, Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF., Cell
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
Tiacci et al., 2011, BRAF mutations in hairy-cell leukemia., N. Engl. J. Med.
Chen et al., 2014, BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis., PLoS ONE
2016, Triple Therapy Improves Colorectal Cancer Response., Cancer Discov
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.
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
Larkin et al., 2014, Combined vemurafenib and cobimetinib in BRAF-mutated melanoma., N. Engl. J. Med.
Chen et al., 2016, Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120., Cancer Discov
Falchook et al., 2012, Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial., Lancet Oncol.
De Roock et al., 2009, Clinical biomarkers in oncology: focus on colorectal cancer., Mol Diagn Ther
Maldonado et al., 2003, Determinants of BRAF mutations in primary melanomas., J. Natl. Cancer Inst.
Hargrave DR et al., 2019, Efficacy and Safety of Dabrafenib in Pediatric Patients with <i>BRAF</i> V600 Mutation-Positive Relapsed or Refractory Low-Grade Glioma: Results from a Phase I/IIa Study., Clin Cancer Res
Fioravanti et al., 1976, Pyridine nucleotide transhydrogenases of parasitic helminths., Arch. Biochem. Biophys.
Flaherty et al., 2012, Improved survival with MEK inhibition in BRAF-mutated melanoma., N. Engl. J. Med.
Haldar et al., 2011, Epidermal growth factor receptor blockers for the treatment of ovarian cancer., Cochrane Database Syst Rev
Nicolaides et al., 2011, Targeted therapy for BRAFV600E malignant astrocytoma., Clin. Cancer Res.
Planchard et al., 2016, Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial., Lancet Oncol.
Shen et al., 2016, Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma., Nat. Med.
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
Gibney et al., 2013, Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies., Expert Opin Drug Metab Toxicol
Karoulia et al., 2016, An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling., Cancer Cell
Davies et al., 2002, Mutations of the BRAF gene in human cancer., Nature
Long et al., 2016, Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib., J. Clin. Oncol.
Klempner et al., 2016, BRAFV600E Mutations in High-Grade Colorectal Neuroendocrine Tumors May Predict Responsiveness to BRAF-MEK Combination Therapy., Cancer Discov
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
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.
Walczyk et al., 2014, The BRAF(V600E) mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?, Clin. Endocrinol. (Oxf)
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.
Menzies et al., 2014, Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma., Clin. Cancer Res.
Ponti et al., 2012, Overwhelming response to Dabrafenib in a patient with double BRAF mutation (V600E; V600M) metastatic malignant melanoma., J Hematol Oncol
Long et al., 2014, Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma., N. Engl. J. Med.
Hauschild et al., 2012, Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial., Lancet
Loaiza-Bonilla A et al., 2014, Dramatic response to dabrafenib and trametinib combination in a BRAF V600E-mutated cholangiocarcinoma: implementation of a molecular tumour board and next-generation sequencing for personalized medicine., Ecancermedicalscience
Kurman et al., 2011, Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm., Hum. Pathol.
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.
Agarwal et al., 2016, Response to Targeted Therapy in BRAF Mutant Anaplastic Thyroid Cancer., J Natl Compr Canc Netw
Chapman et al., 2011, Improved survival with vemurafenib in melanoma with BRAF V600E mutation., N. Engl. J. Med.
Prahallad et al., 2012, Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR., Nature
Sen et al., 2012, Kinase-impaired BRAF mutations in lung cancer confer sensitivity to dasatinib., Sci Transl Med
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.
Crescenzi et al., 2014, Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers., Horm. Metab. Res.
Ascierto et al., 2013, Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma., J. Clin. Oncol.
Garner et al., 1975, Effect of pH on substrate and inhibitor kinetic constants of human liver alanine aminopeptidase. Evidence for two ionizable active center groups., Biochemistry
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
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.
Hatzivassiliou et al., 2013, Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers., Nature
Yang et al., 2012, Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer., Cancer Res.
Noeparast A et al., 2016, Non-V600 BRAF mutations recurrently found in lung cancer predict sensitivity to the combination of Trametinib and Dabrafenib., Oncotarget
Kocsis J et al., 2017, Combined dabrafenib and trametinib treatment in a case of chemotherapy-refractory extrahepatic BRAF V600E mutant cholangiocarcinoma: dramatic clinical and radiological response with a confusing synchronic new liver lesion., J Gastrointest Oncol
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
Corcoran et al., 2015, Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer., J. Clin. Oncol.
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
Drobysheva et al., 2017, Targeted MAPK Pathway Inhibitors in Patients With Disseminated Pilocytic Astrocytomas., J Natl Compr Canc Netw
Nakayama et al., 2008, KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer., Br. J. Cancer
Nagore et al., 2014, Prognostic value of BRAF mutations in localized cutaneous melanoma., J. Am. Acad. Dermatol.
Rad et al., 2013, A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention., Cancer Cell
Hirschi et al., 2014, Genetic targeting of B-RafV600E affects survival and proliferation and identifies selective agents against BRAF-mutant colorectal cancer cells., Mol. Cancer
Poole-Wilson et al., 1975, Effect of pH on ionic exchange and function in rat and rabbit myocardium., Am. J. Physiol.
Morris et al., 2013, Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors., Cancer Discov
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
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.
Naoki et al., 2002, Missense mutations of the BRAF gene in human lung adenocarcinoma., Cancer Res.
Zecchin et al., 2013, BRAF V600E is a determinant of sensitivity to proteasome inhibitors., Mol. Cancer Ther.
Brose et al., 2002, BRAF and RAS mutations in human lung cancer and melanoma., Cancer Res.
Long GV et al., 2017 Sep 10, Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma., N Engl J Med
Oddo et al., 2016, Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer., Cancer Res.
Howell et al., 2011, Both BRAF V600E mutation and older age (≥ 65 years) are associated with recurrent papillary thyroid cancer., Ann. Surg. Oncol.
Sakaguchi et al., 1976, Microbiological oxidation of synthetic chalcocite and covellite by Thiobacillus ferrooxidans., Appl. Environ. Microbiol.
Tejpar et al., 2010, Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery., Oncologist
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
Corcoran RB et al., 2018, Combined BRAF, EGFR, and MEK Inhibition in Patients with <i>BRAF</i><sup>V600E</sup>-Mutant Colorectal Cancer., Cancer Discov
Dienstmann et al., 2011, BRAF as a target for cancer therapy., Anticancer Agents Med Chem
Lavingia V et al., 2016, Impressive response to dual <i>BRAF</i> and MEK inhibition in patients with BRAF mutant intrahepatic cholangiocarcinoma-2 case reports and a brief review., J Gastrointest Oncol
Boulalas et al., Mutational analysis of the BRAF gene in transitional cell carcinoma of the bladder., Int. J. Biol. Markers
Gautschi et al., 2012, A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib., J Thorac Oncol
He et al., 2014, Prognostic value of the BRAF V600E mutation in papillary thyroid carcinoma., Oncol Lett
Patel et al., 2013, Clinical responses to selumetinib (AZD6244; ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma., Cancer
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.
Ho et al., 2013, Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer., N. Engl. J. Med.
Dienstmann et al., 2015, Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors., Cancer Discov
Planchard et al., 2016, Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial., Lancet Oncol.
Wagle et al., 2014, MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition., Cancer Discov
Silen et al., 1975, Acid-base balance in amphibian gastric mucosa., Am. J. Physiol.
Watson et al., 2014, The RAC1 P29S hotspot mutation in melanoma confers resistance to pharmacological inhibition of RAF., Cancer Res.
Kulkarni D et al., 2016, Pyrexia in dabrafenib-treated melanoma patients is not associated with common genetic variation or HLA polymorphisms., Pharmacogenomics
Rizos et al., 2014, BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact., Clin. Cancer Res.
Maertens et al., 2013, Elucidating distinct roles for NF1 in melanomagenesis., Cancer Discov
Souroullas et al., 2016, An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation., Nat. Med.
Wang et al., 2017, ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition., Cell Rep

DABRAFENIB BRAF

Interaction Score: 3.55

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Response Type predicted – resistant

Indication/Tumor Type ovarian cancer

combination therapy AMG 232 + Trametinib + Dabrafenib

PMIDs:
23020132 22608338 26619011 21483012 24265155 22351686 29072975 19001320 27659046 21156289 25370473 20368568 27797976 19255327 22048237 19561230 19010912 23549875 25024077 23489023 27255157 18541894 24586605 24508103 28268064 22773810 2013 23833300 23812671 25399551 24576830 19238210 20818844 24265153 23463675 23612012 25673644 28512244 23251002 25452114 22356324 20857202 22536370 22997239 21163703 15035987 23470635 21663470 24594804 27770002 22586120 20413299 25265494 26732095 22805292 19537845 14679157 31811016 8009 22663011 21975775 22038996 27283860 27500726 22448344 23621583 27523909 12068308 26811525 27048246 24163374 19773371 24354346 23325582 24583796 23031422 25265492 22735384 25435907 21683865 25370471 27697975 21639808 22281684 22649091 22241789 24570209 23918947 38 25989278 22389471 23934108 22180495 28947956 28480077 23524406 26392102 26678033 28784858 19018267 24388723 23845441 24885690 2014 23614898 25157968 20619739 12460919 24107445 12460918 28891408 27312529 21594703 8006 20350999 20630094 29431699 21426297 28078132 19404918 22743296 24396464 22972589 21129611 23406027 25656898 27080216 24265154 2015

Sources:
CancerCommons MyCancerGenomeClinicalTrial OncoKB FDA PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank COSMIC TALC MyCancerGenome GuideToPharmacology CGI
DABRAFENIB ATXN1L

Interaction Score: 1.65

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
28178529

Sources:
CIViC
DABRAFENIB NEK11

Interaction Score: 1.23

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
DrugBank
DABRAFENIB RAC1

Interaction Score: 0.74

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
25056119 24265153

Sources:
CIViC
DABRAFENIB EZH2

Interaction Score: 0.62

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
27135738

Sources:
CIViC
DABRAFENIB STAG2

Interaction Score: 0.62

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trametinib + Dabrafenib

Indication/Tumor Type melanoma

Response Type decreased response

PMIDs:
27500726

Sources:
JAX-CKB
DABRAFENIB SIK1

Interaction Score: 0.62

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
DrugBank
DABRAFENIB MAP2K1

Interaction Score: 0.41

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dabrafenib + SCH772984

Indication/Tumor Type colorectal cancer

Response Type sensitive

PMIDs:
25370473 24265153 25673644 22389471 27312529 24463458 24265154

Sources:
JAX-CKB CIViC
DABRAFENIB NRAS

Interaction Score: 0.31

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trametinib + Dabrafenib

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
25452114 27523909 22389471

Sources:
PharmGKB JAX-CKB CIViC
DABRAFENIB NF1

Interaction Score: 0.24

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23171796

Sources:
CIViC
DABRAFENIB CDKN2A

Interaction Score: 0.22

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24265155

Sources:
CIViC
DABRAFENIB MAP2K2

Interaction Score: 0.17

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24265153 25452114

Sources:
CIViC
DABRAFENIB HLA-DRB1

Interaction Score: 0.16

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
27023328

Sources:
PharmGKB
DABRAFENIB G6PD

Interaction Score: 0.1

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family BRAF inhibitor

Alteration G6PD:.

Alteration G6PD:S218F

PMIDs:
None found

Sources:
FDA PharmGKB CGI
DABRAFENIB LIMK1

Interaction Score: 0.1

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
DrugBank
DABRAFENIB MITF

Interaction Score: 0.09

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24265153

Sources:
CIViC
DABRAFENIB RAF1

Interaction Score: 0.09

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

PMIDs:
None found

Sources:
DrugBank
DABRAFENIB HRAS

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
PharmGKB
DABRAFENIB AKT1

Interaction Score: 0.06

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24265155

Sources:
CIViC
DABRAFENIB KRAS

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Dabrafenib + Trametinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

PMIDs:
27312529

Sources:
PharmGKB JAX-CKB
DABRAFENIB PIK3CA

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dabrafenib + Everolimus + Trametinib

Indication/Tumor Type thyroid carcinoma

Response Type sensitive

PMIDs:
27797976

Sources:
JAX-CKB
DABRAFENIB EGFR

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trametinib + Dabrafenib

Indication/Tumor Type colorectal cancer

Response Type resistant

PMIDs:
27312529

Sources:
JAX-CKB
DABRAFENIB TP53

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy ABT-263 + CGM097 + Dabrafenib + PF-04217903

Indication/Tumor Type colorectal cancer

Response Type sensitive

PMIDs:
27659046

Sources:
JAX-CKB

DrugBank: DB08912
- Version: 5.1.7
Alternate Names:

DABRAFENIB DrugBank Drug Name

1195765-45-7 CAS Number

Tafinlar Drug Brand

Drug Info:

Drug Groups approved

Drug Type small molecule

Drug Groups investigational

Publications:

Gibney et al., 2013, Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies., Expert Opin Drug Metab Toxicol
CancerCommons: DABRAFENIB
- Version: 25-July-2013
Alternate Names:

44462760 PubChem Drug ID

Dabrafenib Drug Trade Name

Dabrafenib Drug Development Name

Drug Info:

Drug Class RAF Inhibitor

Source Reported Drug Name(s) Dabrafenib/GSK2118436

Pharmaceutical Developer GlaxoSmithKline

Publications:
MyCancerGenome: DABRAFENIB
- Version: 20-Jun-2017
Alternate Names:

DABRAFENIB Generic Name

Drug Info:

Drug Class Kinase Inhibitors

FDA Approval Melanoma (with BRAF V600 mutation)

Publications:
TdgClinicalTrial: GSK2118436
- Version: January-2014
Alternate Names:

Drug Info:

Drug Indications antineoplastic agent

Drug Class Small molecule

FDA Approval not approved

Publications:

CGI: Dabrafenib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

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

Kim et al., 2013, Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation., Thyroid

Bland et al., 1976, Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial., Am. J. Obstet. Gynecol.

JAX-CKB: Dabrafenib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Carlino et al., 2015, Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic melanoma patients., Clin. Cancer Res.

Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov

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.

DoCM: DABRAFENIB

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.

PharmGKB: dabrafenib
- Version: 18-August-2020
Alternate Names:

Drug Info:

Publications:

Kulkarni D et al., 2016, Pyrexia in dabrafenib-treated melanoma patients is not associated with common genetic variation or HLA polymorphisms., Pharmacogenomics

CIViC: DABRAFENIB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Van Allen et al., 2014, The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma., Cancer Discov

Ahronian et al., 2015, Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations., Cancer Discov

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

TALC: DABRAFENIB
- Version: 12-May-2016
Alternate Names:

DABRAFENIB Primary Drug Name

DABRAFENIB Drug Generic Name

TAFINLAR Drug Trade Name

Drug Info:

Publications:
TTD: Dabrafenib
- Version: 2020.06.01
Alternate Names:

D05ROI TTD Drug ID

Drug Info:

Publications:
GuideToPharmacology: 178103108
- Version: 29-September-2020
Alternate Names:

DABRAFENIB GuideToPharmacology Ligand Name

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL2028663
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
MyCancerGenomeClinicalTrial: GSK2118436
- Version: 30-February-2014
Alternate Names:

Drug Info:

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

Drug Info:

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

Drug Info:

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

Drug Info:

Publications:

Response Type	predicted – resistant
Indication/Tumor Type	ovarian cancer
combination therapy	AMG 232 + Trametinib + Dabrafenib

combination therapy	Trametinib + Dabrafenib
Indication/Tumor Type	melanoma
Response Type	decreased response

combination therapy	Dabrafenib + SCH772984
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

Drug family	BRAF inhibitor
Alteration	G6PD:.
Alteration	G6PD:S218F

combination therapy	Cetuximab + Dabrafenib + Trametinib
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

combination therapy	Dabrafenib + Everolimus + Trametinib
Indication/Tumor Type	thyroid carcinoma
Response Type	sensitive

combination therapy	ABT-263 + CGM097 + Dabrafenib + PF-04217903
Indication/Tumor Type	colorectal cancer
Response Type	sensitive

DABRAFENIB	DrugBank Drug Name
1195765-45-7	CAS Number
Tafinlar	Drug Brand

Drug Groups	approved
Drug Type	small molecule
Drug Groups	investigational

44462760	PubChem Drug ID
Dabrafenib	Drug Trade Name
Dabrafenib	Drug Development Name

antagonist (inhibitory)
inhibitor (inhibitory)

antagonist (inhibitory)
inhibitor (inhibitory)

antagonist (inhibitory)
inhibitor (inhibitory)

antagonist (inhibitory)
inhibitor (inhibitory)

DABRAFENIB	Primary Drug Name
DABRAFENIB	Drug Generic Name
TAFINLAR	Drug Trade Name

DABRAFENIB Drug Record

DABRAFENIB chembl:CHEMBL2028663 ApprovedAntineoplastic

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info: Response Type predicted – resistant Indication/Tumor Type ovarian cancer combination therapy AMG 232 + Trametinib + Dabrafenib

Sources: CancerCommons MyCancerGenomeClinicalTrial OncoKB FDA PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank COSMIC TALC MyCancerGenome GuideToPharmacology CGI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 28178529

Sources: CIViC

Interaction Types & Directionality: antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info:

PMIDs: None found

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 25056119 24265153

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 27135738

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Trametinib + Dabrafenib Indication/Tumor Type melanoma Response Type decreased response

PMIDs: 27500726

Sources: JAX-CKB

Interaction Types & Directionality: antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info:

PMIDs: None found

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Dabrafenib + SCH772984 Indication/Tumor Type colorectal cancer Response Type sensitive

PMIDs: 25370473 24265153 25673644 22389471 27312529 24463458 24265154

Sources: JAX-CKB CIViC

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Trametinib + Dabrafenib Indication/Tumor Type melanoma Response Type sensitive

PMIDs: 25452114 27523909 22389471

Sources: PharmGKB JAX-CKB CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 23171796

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24265155

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24265153 25452114

Sources: CIViC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 27023328

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info: Drug family BRAF inhibitor Alteration G6PD:. Alteration G6PD:S218F

PMIDs: None found

Sources: FDA PharmGKB CGI

Interaction Types & Directionality: antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info:

PMIDs: None found

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24265153

Sources: CIViC

Interaction Types & Directionality: antagonist (inhibitory) inhibitor (inhibitory)

Interaction Info:

PMIDs: None found

Sources: DrugBank

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24265155

Sources: CIViC

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

Interaction Info:

Response Type predicted – resistant

Indication/Tumor Type ovarian cancer

combination therapy AMG 232 + Trametinib + Dabrafenib

Sources:
CancerCommons MyCancerGenomeClinicalTrial OncoKB FDA PharmGKB DoCM JAX-CKB TdgClinicalTrial CIViC TTD DrugBank COSMIC TALC MyCancerGenome GuideToPharmacology CGI

Interaction Types & Directionality:

n/a

PMIDs:
28178529

Sources:
CIViC

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

PMIDs:
None found

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
25056119 24265153

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
27135738

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trametinib + Dabrafenib

Indication/Tumor Type melanoma

Response Type decreased response

PMIDs:
27500726

Sources:
JAX-CKB

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

PMIDs:
None found

Sources:
DrugBank

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dabrafenib + SCH772984

Indication/Tumor Type colorectal cancer

Response Type sensitive

PMIDs:
25370473 24265153 25673644 22389471 27312529 24463458 24265154

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trametinib + Dabrafenib

Indication/Tumor Type melanoma

Response Type sensitive

PMIDs:
25452114 27523909 22389471

Sources:
PharmGKB JAX-CKB CIViC

Interaction Types & Directionality:

n/a

PMIDs:
23171796

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
24265155

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
24265153 25452114

Sources:
CIViC

Interaction Types & Directionality:

n/a

PMIDs:
27023328

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family BRAF inhibitor

Alteration G6PD:.

Alteration G6PD:S218F

PMIDs:
None found

Sources:
FDA PharmGKB CGI

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

PMIDs:
None found

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
24265153

Sources:
CIViC

Interaction Types & Directionality:

antagonist (inhibitory)

inhibitor (inhibitory)

PMIDs:
None found

Sources:
DrugBank

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
24265155

Sources:
CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Cetuximab + Dabrafenib + Trametinib

Indication/Tumor Type colorectal cancer

Response Type sensitive

PMIDs:
27312529

Sources:
PharmGKB JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Dabrafenib + Everolimus + Trametinib

Indication/Tumor Type thyroid carcinoma

Response Type sensitive

PMIDs:
27797976

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Trametinib + Dabrafenib

Indication/Tumor Type colorectal cancer

Response Type resistant

PMIDs:
27312529

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy ABT-263 + CGM097 + Dabrafenib + PF-04217903

Indication/Tumor Type colorectal cancer

Response Type sensitive

PMIDs:
27659046

Sources:
JAX-CKB

Alternate Names:

DABRAFENIB DrugBank Drug Name

1195765-45-7 CAS Number

Tafinlar Drug Brand

Drug Info:

Drug Groups approved

Drug Type small molecule

Drug Groups investigational

Publications:

Gibney et al., 2013, Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies., Expert Opin Drug Metab Toxicol