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Dabrafenib

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Also known as GSK-2118436GSK-2118436AGsk2118436GSK2118436ATafinlarSID174006404DabrafenibDABRAFENIB (GSK2118436)

Summary

Dabrafenib (CHEMBL2028663) is an approved small-molecule antineoplastic agent (ATC L01EC02) targeting BRAF; indicated across 22 conditions including neoplasm and melanoma; with CIViC clinical evidence for 75 variant-indication associations (e.g. BRAF V600E in melanoma).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01EC02
  • Targets: 1 (BRAF)
  • Indications: 22 conditions
  • Clinical trials: 138
  • Precision-oncology evidence (CIViC): 75 variant–indication associations
  • Chemistry: 519.6 Da · C23H20F3N5O2S2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL2028663
NameDabrafenib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID44462760
ChEBICHEBI:75045
ATCL01EC02
Molecular formulaC23H20F3N5O2S2
Molecular weight519.6
InChIKeyBFSMGDJOXZAERB-UHFFFAOYSA-N

SMILES: CC(C)(C)C1=NC(=C(S1)C2=NC(=NC=C2)N)C3=C(C(=CC=C3)NS(=O)(=O)C4=C(C=CC=C4F)F)F

IUPAC name: N-[3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide

ChEBI definition: An organofluorine compound and antineoplastic agent, used as its mesylate salt in treatment of metastatic melanoma.

Pharmacological roles (ChEBI): antineoplastic agent, B-Raf inhibitor, anticoronaviral agent.

Also known as: Dabrafenib, GSK-2118436, GSK-2118436A, Gsk2118436, GSK2118436A, Tafinlar, DABRAFENIB, SID174006404, dabrafenib, Dabrafenib; Tafinlar, DABRAFENIB (GSK2118436), Dabrafenib (GSK2118436)

Parent form; salt/anhydrous children: CHEMBL2105729

Patent coverage: 5,107 distinct patent families (12,430 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 11,720 (94%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
BRAFB-Raf proto-oncogene, serine/threonine kinaseInhibition8.498.6%P15056

Broader ChEMBL bioactivity targets: 55 (assay-derived). Sample: Serine/threonine-protein kinase/endoribonuclease IRE1, Serine/threonine-protein kinase A-Raf, Receptor-interacting serine/threonine-protein kinase 3, Tyrosine-protein kinase Fyn, Tyrosine-protein kinase ABL1, RAF proto-oncogene serine/threonine-protein kinase, Dual serine/threonine and tyrosine protein kinase, Tyrosine-protein kinase Yes, GTPase KRas, Calcium/calmodulin-dependent protein kinase type IV.

Bioactivity

ChEMBL activities: 91 potent at pChembl ≥ 5 of 93 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
BRAF9.4IC500.4nMCHEMBL_ACT_16577174
BRAF9.3IC500.5nMCHEMBL_ACT_22885302
BRAF9.3IC500.5nMCHEMBL_ACT_24882866
BRAF9.22IC500.6nMCHEMBL_ACT_25708394
BRAF9.19IC500.65nMCHEMBL_ACT_26027115
BRAF9.15IC500.7nMCHEMBL_ACT_12691522
BRAF9.15IC500.7nMCHEMBL_ACT_18745643
BRAF9.15IC500.71nMCHEMBL_ACT_18745826
BRAF9.15IC500.7nMCHEMBL_ACT_22892178
BRAF9.15IC500.7nMCHEMBL_ACT_22929313
BRAF9.15EC500.7nMCHEMBL_ACT_24882829
BRAF9.15IC500.7nMCHEMBL_ACT_29065633
BRAF9.1IC500.8nMCHEMBL_ACT_18528065
BRAF9IC501nMCHEMBL_ACT_16577212
BRAF9IC501nMCHEMBL_ACT_16578214
RIPK38.7IC502nMCHEMBL_ACT_19146734
BRAF8.7IC502nMCHEMBL_ACT_26023197
BRAF8.49IC503.2nMCHEMBL_ACT_26023196
BRAF8.49IC503.2nMCHEMBL_ACT_26027106
BRAF8.4IC504nMCHEMBL_ACT_12691436
BRAF8.4IC504nMCHEMBL_ACT_12691510
BRAF8.4IC504nMCHEMBL_ACT_18528064
BRAF8.3IC505nMCHEMBL_ACT_18946042
RAF18.3IC505nMCHEMBL_ACT_25708393
BRAF8.3IC505nMCHEMBL_ACT_25874433
RAF18.3IC505nMCHEMBL_ACT_26027101
BRAF8.22IC506nMCHEMBL_ACT_15605136
BRAF8.1IC508nMCHEMBL_ACT_12691441
BRAF8.05IC509nMCHEMBL_ACT_16673781
BRAF8.01IC509.7nMCHEMBL_ACT_15605028

Target pathways

Aggregated over 1 target gene(s): BRAF.

Top Reactome pathways

39 total, by targets touching each:

PathwayTargetsGenes
Spry regulation of FGF signaling1BRAF
Signal Transduction1BRAF
Disease1BRAF
Signaling by NTRKs1BRAF
Prolonged ERK activation events1BRAF
Frs2-mediated activation1BRAF
ARMS-mediated activation1BRAF
Signaling by NTRK1 (TRKA)1BRAF
Signalling to ERKs1BRAF
Signalling to p38 via RIT and RIN1BRAF
Signaling by FGFR1BRAF
Negative regulation of FGFR1 signaling1BRAF
Negative regulation of FGFR2 signaling1BRAF
Negative regulation of FGFR3 signaling1BRAF
Negative regulation of FGFR4 signaling1BRAF
Signaling by FGFR11BRAF
Signaling by FGFR21BRAF
Signaling by FGFR31BRAF
Signaling by FGFR41BRAF
Diseases of signal transduction by growth factor receptors and second messengers1BRAF
RAF activation1BRAF
RAF/MAP kinase cascade1BRAF
MAP2K and MAPK activation1BRAF
Negative feedback regulation of MAPK pathway1BRAF
Negative regulation of MAPK pathway1BRAF
MAPK family signaling cascades1BRAF
MAPK1/MAPK3 signaling1BRAF
Signaling by moderate kinase activity BRAF mutants1BRAF
Signaling by high-kinase activity BRAF mutants1BRAF
Signaling by RAS mutants1BRAF

Dominant GO biological processes

GO termTargets
MAPK cascade1
myeloid progenitor cell differentiation1
protein phosphorylation1
epidermal growth factor receptor signaling pathway1
visual learning1
animal organ morphogenesis1
positive regulation of gene expression1
negative regulation of fibroblast migration1
positive regulation of D-glucose transmembrane transport1
synaptic vesicle exocytosis1
thyroid gland development1
T cell differentiation in thymus1
positive regulation of peptidyl-serine phosphorylation1
substrate adhesion-dependent cell spreading1
somatic stem cell population maintenance1

Indications & clinical

Indications

22 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
neoplasm4MONDO:0005070EFO:0000616
melanoma3MONDO:0005105EFO:0000756
cutaneous melanoma3MONDO:0005012EFO:0000389
thyroid gland papillary carcinoma3MONDO:0005075EFO:0000641
metastatic melanoma3MONDO:0005191EFO:0002617
thyroid gland carcinoma3MONDO:0015075EFO:0002892
ameloblastoma3MONDO:0017795MONDO:0017795
thyroid gland follicular carcinoma2MONDO:0005034EFO:0000501
non-small cell lung carcinoma2MONDO:0005233EFO:0003060
Erdheim-Chester disease2MONDO:0018153EFO:1000926
lung neoplasm2MONDO:0021117MONDO:0008903
undifferentiated carcinoma2MONDO:0005617EFO:0006772
craniopharyngioma2MONDO:0018907EFO:1000209
thyroid gland undifferentiated (anaplastic) carcinoma2MONDO:0006468EFO:1000595
liver disorder1MONDO:0005154EFO:0001421
brain neoplasm1MONDO:0021211EFO:0003833
plasma cell myeloma1MONDO:0009693EFO:0001378
kidney disorder1MONDO:0005240EFO:0003086
glioma1MONDO:0021042MONDO:0100342

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 138.

Phase distribution

PhaseTrials
PHASE260
PHASE131
Not specified19
PHASE1/PHASE213
PHASE310
PHASE43
PHASE2/PHASE32

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03340506PHASE4RECRUITINGDabrafenib and/or Trametinib Rollover Study
NCT03975829PHASE4RECRUITINGPediatric Long-Term Follow-up and Rollover Study
NCT07010393PHASE4NOT_YET_RECRUITINGGenotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study
NCT04940052PHASE3ACTIVE_NOT_RECRUITINGStudy of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Previously Treated Patients With Metastatic, Radio-active Iodine Refractory BRAF V600E Mutation Positive Differentiated Thyroid Cancer
NCT06475989PHASE3RECRUITINGStudy of Targeted Therapy vs. Chemotherapy in Patients With Thyroid Cancer
NCT06819605PHASE2/PHASE3NOT_YET_RECRUITINGNeoadjuvant Therapy With Conservative Surgery vs. Up-front Conservative Surgery for BRAF V600E-Mutated Ameloblastoma
NCT07440290PHASE2/PHASE3NOT_YET_RECRUITINGDETERMINE Trial Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and Teenage/Young Adult Patients With BRAF V600 Mutation-Positive Cancers.
NCT01227889PHASE3COMPLETEDA Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma
NCT01584648PHASE3COMPLETEDA Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma
NCT01597908PHASE3COMPLETEDDabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma
NCT01682083PHASE3COMPLETEDDabrafenib With Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma (COMBI-AD).
NCT02967692PHASE3TERMINATEDA Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma
NCT03551626PHASE3COMPLETEDStudy of Dabrafenib+Trametinib in the Adjuvant Treatment of Stage III BRAF V600+ Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes
NCT03784014PHASE3COMPLETEDMolecular Profiling of Advanced Soft-tissue Sarcomas
NCT06264778PHASE3UNKNOWNExploration of Fenestration Decompression Combined With Dalafenib in the Treatment of BRAF Mutant Ameloblastoma
NCT01972347PHASE2ACTIVE_NOT_RECRUITINGNeoadjuvant Dabrafenib + Trametinib for AJCC Stage IIIB-C BRAF V600 Mutation Positive Melanoma
NCT01989585PHASE1/PHASE2ACTIVE_NOT_RECRUITINGTesting the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma
NCT02231775PHASE2ACTIVE_NOT_RECRUITINGDabrafenib and Trametinib Before and After Surgery in Treating Patients With Stage IIIB-C Melanoma With BRAF V600 Mutation
NCT02465060PHASE2ACTIVE_NOT_RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
NCT02910700PHASE2ACTIVE_NOT_RECRUITINGNivolumab With Trametinib and Dabrafenib, or Encorafenib and Binimetinib in Treating Patients With BRAF Mutated Metastatic or Unresectable Stage III-IV Melanoma
NCT02925234PHASE2RECRUITINGThe Drug Rediscovery Protocol (DRUP Trial)
NCT03149029PHASE2ACTIVE_NOT_RECRUITINGAbbreviated MAPK Targeted Therapy Plus Pembrolizumab in Melanoma
NCT03563729PHASE2RECRUITINGMelanoma Metastasized to the Brain and Steroids
NCT04116541PHASE2RECRUITINGA Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors.
NCT04201457PHASE1/PHASE2ACTIVE_NOT_RECRUITINGA Trial of Dabrafenib, Trametinib and Hydroxychloroquine for Patients With Recurrent LGG or HGG With a BRAF Aberration
NCT04238624PHASE2ACTIVE_NOT_RECRUITINGStudy of Cemiplimab Combined With Dabrafenib and Trametinib in People With Anaplastic Thyroid Cancer
NCT04544111PHASE2ACTIVE_NOT_RECRUITINGPDR001 Combination Therapy for Radioiodine-Refractory Thyroid Cancer
NCT04675710PHASE2ACTIVE_NOT_RECRUITINGPembrolizumab, Dabrafenib, and Trametinib Before Surgery for the Treatment of BRAF-Mutated Anaplastic Thyroid Cancer
NCT05159245PHASE2RECRUITINGThe Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs
NCT05525273PHASE2RECRUITINGTreatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma
NCT06054191PHASE2NOT_YET_RECRUITINGNeoadjuvant and Adjuvant Targeted Treatment in NSCLC With BRAF V600 or MET Exon 14 Mutations
NCT06079333PHASE2RECRUITINGNEO- and Adjuvant Targeted Therapy in Braf-mutated Anaplastic Cancer of the Thyroid (NEO-ATACT Study)
NCT06119789PHASE2RECRUITINGPrecision Cancer Therapy in Rare Cancers
NCT06362694PHASE2RECRUITINGStudy of the Rechallenge Concept in Patients With BRAF-positive Anaplastic Thyroid Cancer After Progression on Anti-BRAF Therapy
NCT06482086PHASE2RECRUITINGEfficacy of Organoid-Based Drug Screening to Guide Treatment for Locally Advanced Thyroid Cancer
NCT06563999PHASE2RECRUITINGNeoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.
NCT06653517PHASE2RECRUITINGClinical Study of Neoadjuvant Targeted Therapy for Ameloblastoma
NCT06712875PHASE1/PHASE2RECRUITINGMAPK Inhibition Combined With Anti-PD1 Therapy for BRAF-altered Pediatric Gliomas
NCT06739395PHASE2RECRUITINGPrecision Medicine Trial Based on Molecular Matching Therapy for Patients With Standard Treatment Exhaustion
NCT07110246PHASE2RECRUITINGDabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas

Clinical evidence (CIViC)

Variant × indication × effect (75 predictive associations from 89 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
BRAF V600EMelanomaSensitivity/ResponseDabrafenibCIViC AEID11244 +5
BRAF V600EPleomorphic XanthoastrocytomaSensitivity/ResponseDabrafenib + TrametinibCIViC AEID11312 +1
BRAF V600Skin MelanomaSensitivity/ResponseDabrafenib + TrametinibCIViC AEID1411
BRAF V600EPilocytic AstrocytomaSensitivity/ResponseDabrafenib + TrametinibCIViC AEID11313
BRAF V600ESolid TumorSensitivity/ResponseTrametinib + DabrafenibCIViC AEID12161
BRAF V600ELow Grade GliomaSensitivity/ResponseDabrafenib + TrametinibCIViC AEID12162
BRAF V600ELung Non-small Cell CarcinomaSensitivity/ResponseDabrafenib + TrametinibCIViC AEID3017
BRAF V600KMelanomaSensitivity/ResponseDabrafenib + TrametinibCIViC BEID6939 +2
BRAF V600MelanomaSensitivity/ResponseDabrafenib + TrametinibCIViC BEID6180 +1
BRAF V600ECholangiocarcinomaSensitivity/ResponseDabrafenib + TrametinibCIViC BEID7453 +1
BRAF V600EMelanomaSensitivity/ResponseDabrafenib + TrametinibCIViC BEID6178 +1
BRAF V600EMelanomaSensitivity/ResponseTrametinib + DabrafenibCIViC BEID6938 +1
BRAF V600KMelanomaSensitivity/ResponseDabrafenibCIViC BEID2505 +1
BRAF K601ESkin MelanomaSensitivity/ResponseDabrafenibCIViC BEID2812
BRAF V600MelanomaSensitivity/ResponseDabrafenibCIViC BEID1407
BRAF V600Colorectal CancerSensitivity/ResponseTrametinib + DabrafenibCIViC BEID1415
BRAF V600Childhood Low-grade GliomaSensitivity/ResponseDabrafenibCIViC BEID8034
BRAF V600MelanomaSensitivity/ResponseTrametinib + DabrafenibCIViC BEID93
BRAF V600DMelanomaSensitivity/ResponseDabrafenibCIViC BEID94
BRAF V600ELangerhans-cell HistiocytosisSensitivity/ResponseDabrafenibCIViC BEID11303
BRAF V600ECancerSensitivity/ResponseTrametinib + DabrafenibCIViC BEID11672
BRAF V600ESkin MelanomaSensitivity/ResponseDabrafenibCIViC BEID2146
BRAF V600ESkin MelanomaSensitivity/ResponseDabrafenib + TrametinibCIViC BEID3758
BRAF V600EColorectal CancerSensitivity/ResponsePanitumumab + Dabrafenib + TrametinibCIViC BEID6123
BRAF V600EAnaplastic Thyroid CarcinomaSensitivity/ResponseDabrafenib + TrametinibCIViC BEID6975
BRAF V600EBiliary Tract CancerSensitivity/ResponseDabrafenib + TrametinibCIViC BEID7264
BRAF V600EOvarian CancerSensitivity/ResponseTrametinib + DabrafenibCIViC BEID7454
BRAF V600EPapillary Thyroid CarcinomaSensitivity/ResponseDabrafenibCIViC BEID7761
BRAF V600EPapillary Thyroid CarcinomaSensitivity/ResponseTrametinib + DabrafenibCIViC BEID7762
BRAF V600KSkin MelanomaSensitivity/ResponseTrametinib + DabrafenibCIViC BEID4181

+45 more predictive associations (showing top 30 by level).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

47 molecules share ≥1 primary target. Top 47 by shared-target count:

MoleculeSourceStatusShared targets
GEFITINIBChEMBL + PubChemPhase 4 (approved)BRAF
PAZOPANIBChEMBL + PubChemPhase 4 (approved)BRAF
REGORAFENIBChEMBL + PubChemPhase 4 (approved)BRAF
ABEMACICLIBChEMBLPhase 4 (approved)BRAF
COBIMETINIBChEMBLPhase 4 (approved)BRAF
DASATINIBChEMBLPhase 4 (approved)BRAF
ENCORAFENIBChEMBLPhase 4 (approved)BRAF
ERLOTINIBChEMBLPhase 4 (approved)BRAF
FEDRATINIBChEMBLPhase 4 (approved)BRAF
IMATINIBChEMBLPhase 4 (approved)BRAF
INFIGRATINIBChEMBLPhase 4 (approved)BRAF
NILOTINIBChEMBLPhase 4 (approved)BRAF
PONATINIBChEMBLPhase 4 (approved)BRAF
RUXOLITINIBChEMBLPhase 4 (approved)BRAF
SORAFENIBChEMBLPhase 4 (approved)BRAF
TOVORAFENIBChEMBLPhase 4 (approved)BRAF
VEMURAFENIBChEMBLPhase 4 (approved)BRAF
AVUTOMETINIBChEMBLPhase 3BRAF
MASITINIBChEMBLPhase 3BRAF
MOTESANIBChEMBLPhase 3BRAF
NAPORAFENIBChEMBLPhase 3BRAF
QUERCETINChEMBLPhase 3BRAF
BAFETINIBChEMBLPhase 2BRAF
BELVARAFENIBChEMBLPhase 2BRAF
BRIMARAFENIBChEMBLPhase 2BRAF
CEP-32496ChEMBLPhase 2BRAF
DORAMAPIMODChEMBLPhase 2BRAF
ELLAGIC ACIDChEMBLPhase 2BRAF
EXARAFENIBChEMBLPhase 2BRAF
FORETINIBChEMBLPhase 2BRAF
LIFIRAFENIBChEMBLPhase 2BRAF
MIRDAMETINIBChEMBLPhase 2BRAF
PEXMETINIBChEMBLPhase 2BRAF
R-406ChEMBLPhase 2BRAF
RAF-265ChEMBLPhase 2BRAF
REBASTINIBChEMBLPhase 2BRAF
TG100-115ChEMBLPhase 2BRAF
TINLORAFENIBChEMBLPhase 2BRAF
XL-281ChEMBLPhase 2BRAF
AfatinibPubChemApprovedBRAF
BinimetinibPubChemApprovedBRAF
CrizotinibPubChemApprovedBRAF
dacomitinibPubChemApprovedBRAF
FostamatinibPubChemApprovedBRAF
IdelalisibPubChemApprovedBRAF
SelumetinibPubChemApprovedBRAF
TrametinibPubChemApprovedBRAF

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot