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Protein / target

Serine/threonine-protein kinase B-raf

Encoded byBRAFP15056Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
8
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Protein serine/threonine kinase

Strongest disease association

Cardiofaciocutaneous syndrome

Via encoding gene BRAF · Genetic evidence · score 0.94

Therapeutic position

Established drug target

Small molecules

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 overview

Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable).

View complete UniProt function annotation

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.

Synaptic signallingUniProt · GOGrowth-factor signallingGOKinase signallingUniProt · GO · Reactome
View supporting evidence

Synaptic signalling

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

Growth-factor signalling

  • ·epidermal growth factor receptor signaling pathway

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
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.

Approved medicines with mapped indications

4 medicines · 4 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Colorectal Neoplasms2 medicines
Melanoma2 medicines
Glioma1 medicine
Broader indication categories (1)

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

8 medicines meet Open Targets' target-level approved-medicine definition; the 4 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

4

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

encorafenib
Narrow target profileApprovedInhibitor

Serine/threonine-protein kinase B-raf inhibitor

Indicated for Colorectal Neoplasms, Melanoma, Neoplasms

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

vemurafenib
Narrow target profileApprovedInhibitor

Serine/threonine-protein kinase B-raf inhibitor

Indicated for Melanoma, Neoplasms

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

regorafenib
ApprovedInhibitor

Serine/threonine-protein kinase B-raf inhibitor

Indicated for Colorectal Neoplasms, Neoplasms

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

tovorafenib
ApprovedInhibitor

RAF serine/threonine protein kinase inhibitor

Indicated for Glioma

Acts on a complex — shared with RAF1, ARAF · 1 of 3 recorded protein targets — narrow recorded profile

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene BRAF

Gene-level evidence surfaced through the gene BRAFthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Melanoma
0.97Well supported

Clinical evidence dominant · Open Targets 0.82

Cardiofaciocutaneous syndrome
0.97Well supported

Genetic evidence dominant · Open Targets 0.88

Cardiofaciocutaneous syndrome 1
0.95Well supported

Genetic evidence dominant · Open Targets 0.76

Colorectal Neoplasms
0.95Well supported

Genetic evidence dominant · Open Targets 0.75

Noonan syndrome 7
0.94Well supported

Genetic evidence dominant · Open Targets 0.76

View evidence synthesis (5)
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 NeoplasmsWell 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 per-type scores above show the calculation.

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 Neoplasms0.75
Neoplasms0.71
Lung Neoplasms0.70

Drug development

18 compounds recorded · 8 approved · 10 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 4 drugs that target this protein in Forefront's canonical graph (4 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
BELVARAFENIBPhase 2
PLIXORAFENIBPhase 2
SORAFENIBApproval
REGORAFENIBApproval
TOVORAFENIBApproval
DABRAFENIB MESYLATEApproval
XL-281Phase 1 2
DABRAFENIBApproval
RG-7256Phase 1
LIFIRAFENIBPhase 1 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (13)
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 DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

heart diseaseForce et al. (2011)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ACTIVE_NOT_RECRUITING · via regorafenib · NCT05395741

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 4 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Label change2026-08-20

    Label change: VEMURAFENIB (NDA202429)

    fda · regulatory · fda · via vemurafenib

  2. Regulatory approval2026-04-20

    Approval: Ojemda (EMA)

    ema · regulatory · ema · via tovorafenib

  3. 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

  4. 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

  5. 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

  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. Regulatory approval2018-09-19

    Approval: Braftovi (EMA)

    ema · regulatory · ema · via encorafenib

  8. Safety communication2015-11-12

    Drug Safety Update: Vemurafenib (Zelboraf▼): risk of potentiation of radiation toxicity

    mhra · safety · mhra · via vemurafenib

  9. Regulatory approval2013-08-26

    Approval: Stivarga (EMA)

    ema · regulatory · ema · via regorafenib

  10. Regulatory approval2012-02-17

    Approval: Zelboraf (EMA)

    ema · regulatory · ema · via vemurafenib

  11. Regulatory approval2011-08-17

    Approval: VEMURAFENIB (NDA202429)

    fda · regulatory · fda · via vemurafenib

  12. New publication2011-06-05
    Improved survival with vemurafenib in melanoma with BRAF V600E mutation.

    The New England journal of medicine · 2011 · 5,684 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.