Protein / target

Serine/threonine-protein kinase B-raf

BRAFP15056Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
8
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Protein serine/threonine kinase activity

Primary system

Nervous system

Strongest disease association

cardiofaciocutaneous syndrome

Genetic evidence · score 0.94

Therapeutic maturity

Clinically validated target

8 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

8 approved · 10 in clinical development

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179)

Subcellular location

NucleusCytoplasmCell membrane
Domains and Gene Ontology detail (33)

Domains & features

RBDProtein kinase

Gene Ontology

  • Ccell body
  • Ccytoplasm
  • Ccytosol
  • Cglutamatergic synapse
  • Cmitochondrion
  • Cneuron projection
  • Cnucleus
  • Cplasma membrane
  • Cpostsynapse
  • FATP binding
  • Fcalcium ion binding
  • Fidentical protein binding

766 aa · 84 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Kinase signallingUniProt · GO · ReactomeSynaptic signallingUniProt · GOExcitatory neurotransmissionGOTranscriptional regulationGOApoptosis & cell deathGO
View supporting evidence

Kinase signalling

  • ·Protein kinase involved in the transduction of mitogenic signals from the cell membrane…
  • ·MAP kinase kinase activity
  • ·MAP kinase kinase kinase activity
  • ·protein kinase activity

Synaptic signalling

  • ·Protein kinase involved in the transduction of mitogenic signals from the cell membrane…
  • ·glutamatergic synapse
  • ·postsynapse
  • ·postsynaptic modulation of chemical synaptic transmission

Excitatory neurotransmission

  • ·glutamatergic synapse

Transcriptional regulation

  • ·positive regulation of gene expression

Apoptosis & cell death

  • ·negative regulation of apoptotic process
View underlying pathways (16)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

YWHAZHRASRAF1KRASNRASMAP2K1HSP90A…MAP2K2ARAFYWHAQBRAF

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

3

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

encorafenib
Narrow target profileApprovedInhibitor

Serine/threonine-protein kinase B-raf inhibitor

Appears in clinical studies involving melanoma, colorectal neoplasm, neoplasm, metastatic melanoma

Direct interaction with this protein · Only this protein recorded as a target

vemurafenib
Narrow target profileApprovedInhibitor

Serine/threonine-protein kinase B-raf inhibitor

Appears in clinical studies involving melanoma, metastatic melanoma, melanoma, neoplasm

Direct interaction with this protein · Only this protein recorded as a target

regorafenib
ApprovedInhibitor

Serine/threonine-protein kinase B-raf inhibitor

Appears in clinical studies involving colorectal cancer, metastatic colorectal cancer, colorectal neoplasm, neoplasm

Direct interaction with this protein · 1 of 18 recorded protein targets — broad pharmacology

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

cardiofaciocutaneous syndrome0.94

Genetic · overall 0.88

cardiofaciocutaneous syndrome 10.94

Genetic · overall 0.76

Noonan syndrome 70.93

Genetic · overall 0.76

LEOPARD syndrome 30.89

Genetic · overall 0.76

Noonan syndrome0.88

Genetic · overall 0.84

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

melanoma0.98

Clinical · overall 0.82

colorectal cancer0.94

Clinical · overall 0.75

cancer0.42

Clinical · overall 0.71

lung cancer0.18

Clinical · overall 0.70

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

Noonan syndrome with multiple lentigines0.75

Genetic literature

Show all associations
cardiofaciocutaneous syndrome0.88
Noonan syndrome0.84
melanoma0.82
cardiofaciocutaneous syndrome 10.76
Noonan syndrome 70.76
LEOPARD syndrome 30.76
Noonan syndrome with multiple lentigines0.75
colorectal cancer0.75
cancer0.71
lung cancer0.70

Open Targets ranks 3,139 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 18 total

BELVARAFENIBPhase 2

central nervous system neoplasm · central nervous system cancer · melanoma

PLIXORAFENIBPhase 2

melanoma · thyroid cancer · neoplasm

SORAFENIBApproval

renal cell carcinoma · hepatocellular carcinoma · renal cell carcinoma

REGORAFENIBApproval

colorectal cancer · metastatic colorectal cancer · colorectal neoplasm

TOVORAFENIBApproval

glioma · low grade glioma · low grade glioma

DABRAFENIB MESYLATEApproval

metastatic melanoma · melanoma · low grade glioma

XL-281Phase 1 2

colorectal cancer · melanoma

DABRAFENIBApproval

melanoma · glioma · neoplasm

RG-7256Phase 1

melanoma · thyroid cancer

LIFIRAFENIBPhase 1 2

endometrial cancer · thyroid cancer · thyroid gland papillary carcinoma

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · Human Protein Atlas locPR · LiteraturePR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life Data

Safety liabilities

heart disease

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Show remaining trials (24)

ACTIVE_NOT_RECRUITING · via regorafenib · NCT05395741

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

melanomaWell supported
0.97
agreement 0.891.00
Clinical32%Genetic31%Somatic mutation23%Pathway8%Literature7%

Open Targets aggregate 0.82 · 5 independent evidence families

cardiofaciocutaneous syndromeWell supported
0.97
agreement 0.871.00
Genetic62%Pathway22%Animal model12%Literature5%Genetic literaturedup

Open Targets aggregate 0.88 · 4 independent evidence families · 1 not counted as duplicate

cardiofaciocutaneous syndrome 1Well supported
0.95
agreement 0.831.00
Genetic85%Animal model14%Literature1%Genetic literaturedup

Open Targets aggregate 0.76 · 3 independent evidence families · 1 not counted as duplicate

colorectal cancerWell supported
0.95
agreement 0.851.00
Genetic44%Clinical40%Literature8%Animal model7%Genetic literaturedup

Open Targets aggregate 0.75 · 4 independent evidence families · 1 not counted as duplicate

Noonan syndrome 7Well supported
0.94
agreement 0.821.00
Genetic87%Animal model12%Literature1%Genetic literaturedup

Open Targets aggregate 0.76 · 3 independent evidence families · 1 not counted as duplicate

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

19

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2025-05-30
    Encorafenib, Cetuximab, and mFOLFOX6 in <i>BRAF</i>-Mutated Colorectal Cancer.

    The New England journal of medicine · 2025 · 55 citations · Europe PMC · via encorafenib

  2. New publication2025-01-25
    Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

    Nature medicine · 2025 · 45 citations · Europe PMC · via encorafenib

  3. New publication2025-01-06
    Efficacy of pembrolizumab in microsatellite-stable, tumor mutational burden-high metastatic colorectal cancer: genomic signatures and clinical outcomes.

    ESMO open · 2025 · 10 citations · Europe PMC · via regorafenib

  4. New publication2024-09-23
    Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial.

    Nature medicine · 2024 · 52 citations · Europe PMC · via encorafenib

  5. New publication2024-09-09
    Efficacy and safety of the combination of encorafenib/cetuximab with or without binimetinib in patients with BRAF V600E-mutated metastatic colorectal cancer: an AGEO real-world multicenter study.

    ESMO open · 2024 · 12 citations · Europe PMC · via encorafenib

  6. New publication2024-06-04
    Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024 · 69 citations · Europe PMC · via regorafenib

  7. New publication2020-08-11
    Targeted therapy for hepatocellular carcinoma.

    Signal transduction and targeted therapy · 2020 · 565 citations · Europe PMC · via regorafenib

  8. New publication2019-11-04
    Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma.

    Journal of experimental & clinical cancer research : CR · 2019 · 162 citations · Europe PMC · via regorafenib

  9. New publication2019-09-30
    Encorafenib, Binimetinib, and Cetuximab in <i>BRAF</i> V600E-Mutated Colorectal Cancer.

    The New England journal of medicine · 2019 · 1,029 citations · Europe PMC · via encorafenib

  10. New publication2019-04-23
    Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019 · 199 citations · Europe PMC · via regorafenib

  11. Regulatory approval2018-09-19

    Approval: Braftovi (EMA)

    ema · regulatory · ema · via encorafenib

  12. New publication2018-03-21
    Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial.

    The Lancet. Oncology · 2018 · 756 citations · Europe PMC · via vemurafenib

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.