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Protein / target

Serine/threonine-protein kinase A-Raf

Encoded byARAFP10398Homo sapiensSwiss-Prot
UniProt: P10398Ensembl: ENSG00000078061HGNC: HGNC:646NCBI Gene: 369
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
10
Clinical trials
Small-molecule tractable
Druggability
Advanced Clinical

Protein at a glance

Biological role

Protein serine/threonine kinase

Strongest disease association

Neoplasms

Via encoding gene ARAF · Pathway evidence · score 0.56

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

Involved in the transduction of mitogenic signals from the cell membrane to the nucleus.

View complete UniProt function annotation

Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade. Phosphorylates PFKFB2 (PubMed:36402789)

Domains and Gene Ontology detail (18)

Domains & features

RBDProtein kinase

Gene Ontology

  • Ccytoplasm
  • Ccytosol
  • Cmitochondrion
  • Cplasma membrane
  • FATP binding
  • FMAP kinase kinase kinase activity
  • Fprotein kinase activity
  • Fprotein serine kinase activity
  • Fprotein serine/threonine kinase activity
  • Fzinc ion binding
  • PMAPK cascade
  • Pnegative regulation of apoptotic process

606 aa · 68 kDa · 2 isoforms

Biological roles

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

Kinase signallingGO
View supporting evidence

Kinase signalling

  • ·MAP kinase kinase kinase activity
  • ·protein kinase activity
  • ·protein serine kinase activity
  • ·protein serine/threonine kinase activity

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

Approved medicines with mapped indications

1 medicine · 1 area

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.

Glioma1 medicine
tovorafenib

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

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.

tovorafenib
ApprovedInhibitor

RAF serine/threonine protein kinase inhibitor

Indicated for Glioma

Acts on a complex — shared with RAF1, BRAF · 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 ARAF

Gene-level evidence surfaced through the gene ARAFthat 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.

Glioma
0.47Limited support

Clinical evidence dominant · Open Targets 0.38

Colorectal adenocarcinoma
0.45Limited support

Pathway evidence dominant · Open Targets 0.28

Neoplasms
0.43Limited support

Pathway evidence dominant · Open Targets 0.56

Adenocarcinoma of Lung
0.41Limited support

Pathway evidence dominant · Open Targets 0.24

Noonan syndrome
0.36Preliminary

Pathway evidence dominant · Open Targets 0.54 · no direct causal or clinical evidence

View evidence synthesis (5)
GliomaLimited support
0.47
agreement 0.32–0.63
Clinical94%Literature6%

Open Targets aggregate 0.38 · 2 independent evidence families

Colorectal adenocarcinomaLimited support
0.45
agreement 0.32–0.58
Pathway60%Somatic mutation39%Literature2%

Open Targets aggregate 0.28 · 3 independent evidence families

NeoplasmsLimited support
0.43
agreement 0.30–0.56
Pathway75%Literature20%Clinical5%

Open Targets aggregate 0.56 · 3 independent evidence families

Adenocarcinoma of LungLimited support
0.41
agreement 0.28–0.54
Pathway52%Somatic mutation38%Literature10%

Open Targets aggregate 0.24 · 3 independent evidence families

Noonan syndromePreliminary
0.36
agreement 0.18–0.54
Pathway99%Literature1%

Open Targets aggregate 0.54 · 2 independent evidence families · no direct causal or clinical evidence

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
Neoplasms0.56
Noonan syndrome0.54
Costello syndrome0.54
Cardiomyopathy, Hypertrophic0.54
Glioma0.38
Colorectal adenocarcinoma0.28
Adenocarcinoma of Lung0.24
Small Cell Lung Carcinoma0.22

Drug development

3 compounds recorded · 1 approved · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (3)
LY-3009120Phase 1
BELVARAFENIBPhase 2
TOVORAFENIBApproval

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 molecules — Strong

Advanced Clinical and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (human protein atlas loc) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · Human Protein Atlas locPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

10

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.

LOGGIC/FIREFLY-2: A Phase 3, Randomized, International Multicenter Trial of DAY101 Monotherapy Versus Standard of Care Chemotherapy in Patients With Pediatric Low-Grade Glioma Harboring an Activating RAF Alteration Requiring First-Line Systemic TherapyPHASE3

ACTIVE_NOT_RECRUITING · via tovorafenib · NCT05566795

A Phase 1 Study of Combination Tovorafenib (DAY101) and Rituximab Treatment in Relapsed or Refractory Classical Hairy Cell Leukemia and Phase 2 Randomized Study Comparing Tovorafenib (DAY101) and Rituximab With Cladribine and Rituximab for Front-Line Treatment of Classical Hairy Cell LeukemiaPHASE1/PHASE2

RECRUITING · via tovorafenib · NCT06965114

A Phase 2 Study of Tovorafenib in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG), Which Harbor Alterations in the Mitogen-Activated Protein Kinase (MAPK) PathwayPHASE2

NOT_YET_RECRUITING · via tovorafenib · NCT07206849

Phase 2 Study of Tovorafenib (DAY101) in Relapsed and Refractory Langerhans Cell HistiocytosisPHASE2

RECRUITING · via tovorafenib · NCT05828069

View all trials (6)
Tovorafenib for the Treatment of Newly Diagnosed or Recurrent Craniopharyngioma in Children and Young AdultsPHASE2

RECRUITING · via tovorafenib · NCT05465174

FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients With RAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid TumorsPHASE2

RECRUITING · via tovorafenib · NCT04775485

A Phase I, Open-label, Single-arm, Multicentre Study to Evaluate the Safety and Pharmacokinetics of Tovorafenib in Japanese Paediatric Participants With BRAF-altered Recurrent or Progressive Low-grade GliomaPHASE1

RECRUITING · via tovorafenib · NCT07441707

VICTORY: A Pilot Study to Investigate Safety and Efficacy of Weekly Combination of Intravenous Vinblastine With Oral Type II RAF Inhibitor Tovorafenib in Pediatric Patients With Recurrent/Progressive RAF Altered Low Grade GliomasEARLY_PHASE1

RECRUITING · via tovorafenib · NCT06381570

A Phase 2, Subprotocol of DAY101 Monotherapy for Patients With Recurrent, Progressive, or Refractory Solid Tumors With MAPK Pathway AberrationsPHASE2

TERMINATED · via tovorafenib · NCT04985604

A Phase 1b/2, Subprotocol of DAY101 in Combination With Pimasertib for Patients With Recurrent, Progressive, or Refractory Solid Tumors and MAPK Pathway AberrationsPHASE1

TERMINATED · via tovorafenib · NCT07121829

ClinicalTrials.gov via the drug-target graph.

What's happening now

1

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets 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. Regulatory approval2026-04-20

    Approval: Ojemda (EMA)

    ema · regulatory · ema · via tovorafenib

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.