Protein / target

Tyrosine-protein kinase FRK

FRKP42685Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Non-membrane spanning protein tyrosine kinase activity

Strongest disease association

gout

Genetic evidence · score 0.61

Therapeutic maturity

Clinically validated target

2 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

2 approved · 4 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

Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents its ubiquitination and degradation, possibly by reducing its binding to NEDD4. May function as a tumor suppressor

Subcellular location

CytoplasmNucleus
Domains and Gene Ontology detail (19)

Domains & features

SH3SH2Protein kinase

Gene Ontology

  • Cazurophil granule lumen
  • Ccytoplasm
  • Ccytosol
  • Cextracellular exosome
  • Cextracellular region
  • Cnucleoplasm
  • Cnucleus
  • Cplasma membrane
  • Cspecific granule lumen
  • FATP binding
  • Fnon-membrane spanning protein tyrosine kinase activity
  • Fprotein tyrosine kinase activity

505 aa · 58 kDa · 2 isoforms

Biological roles

Reactome v97

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

Kinase signallingUniProt · GOTranscriptional regulationGO
View supporting evidence

Kinase signalling

  • ·Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Posit…
  • ·non-membrane spanning protein tyrosine kinase activity
  • ·protein tyrosine kinase activity

Transcriptional regulation

  • ·negative regulation of transcription by RNA polymerase II
View underlying pathways (2)

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.

MIPOL1ASTN2PTENKIAA13…BNIP2ADAMTS…CSKRAPGEF1RPAP2EGFRFRK

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

1

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.

regorafenib
ApprovedInhibitor

Tyrosine-protein kinase FRK 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.

gout0.61

Genetic · overall 0.37

Highest-confidence therapeutic associations

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

chronic myelogenous leukemia, BCR-ABL1 positive0.95

Clinical · overall 0.58

colorectal cancer0.94

Clinical · overall 0.57

acute lymphoblastic leukemia0.89

Clinical · overall 0.54

neoplasm0.77

Clinical · overall 0.49

metastatic colorectal cancer0.67

Clinical · overall 0.41

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

lymphoid leukemia0.41

Clinical

colorectal neoplasm0.37

Clinical

blast phase chronic myelogenous leukemia, BCR-ABL1 positive0.37

Clinical

hepatocellular carcinoma0.37

Clinical

Show all associations
chronic myelogenous leukemia, BCR-ABL1 positive0.58
colorectal cancer0.57
acute lymphoblastic leukemia0.54
neoplasm0.49
metastatic colorectal cancer0.41
lymphoid leukemia0.41
gout0.37
colorectal neoplasm0.37
blast phase chronic myelogenous leukemia, BCR-ABL1 positive0.37
hepatocellular carcinoma0.37

Open Targets ranks 245 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 · 6 total

ILORASERTIBPhase 2

juvenile myelomonocytic leukemia · acute myeloid leukemia · myelodysplastic syndrome

REGORAFENIBApproval

colorectal cancer · metastatic colorectal cancer · colorectal neoplasm

TG100-801Phase 2

macular degeneration · age-related macular degeneration

DASATINIB ANHYDROUSApproval

chronic myelogenous leukemia, BCR-ABL1 positive · acute lymphoblastic leukemia · chronic myelogenous leukemia, BCR-ABL1 positive

ENMD-981693Phase 2

colorectal carcinoma · breast carcinoma · exocrine pancreatic carcinoma

XL-228Phase 1

childhood leukemia · acute lymphoblastic leukemia · chronic myelogenous leukemia, BCR-ABL1 positive

Tractability

SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confPR · Half-life DataPR · Small Molecule Binder

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

TERMINATED · via regorafenib · NCT02402036

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.

chronic myelogenous leukemia, BCR-ABL1 positiveModerately supported
0.71
agreement 0.550.88
Clinical100%

Open Targets aggregate 0.58 · 1 independent evidence family

colorectal cancerModerately supported
0.70
agreement 0.550.86
Clinical100%Literature0%

Open Targets aggregate 0.57 · 2 independent evidence families

acute lymphoblastic leukemiaModerately supported
0.67
agreement 0.520.82
Clinical99%Literature1%

Open Targets aggregate 0.54 · 2 independent evidence families

neoplasmModerately supported
0.61
agreement 0.460.77
Clinical88%Literature12%

Open Targets aggregate 0.49 · 2 independent evidence families

goutModerately supported
0.61
agreement 0.490.73
Genetic100%

Open Targets aggregate 0.37 · 1 independent evidence family

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

7

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

  1. 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

  2. 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

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

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

  4. 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

  5. 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

  6. New publication2016-12-06
    Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial.

    Lancet (London, England) · 2017 · 2,767 citations · Europe PMC · via regorafenib

  7. Regulatory approval2013-08-26

    Approval: Stivarga (EMA)

    ema · regulatory · ema · via regorafenib

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.