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Protein / target

Tyrosine-protein kinase FRK

Encoded byFRKP42685Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Non-membrane spanning protein tyrosine kinase

Strongest disease association

Gout

Via encoding gene FRK · Genetic evidence · score 0.61

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

Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation.

View complete UniProt function annotation

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.

Receptor tyrosine kinase signallingGO
View supporting evidence

Receptor tyrosine kinase signalling

  • ·cell surface receptor protein tyrosine kinase signaling pathway
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.

Approved medicines with mapped indications

1 medicine · 2 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 Neoplasms1 medicine
Broader indication categories (1)
Neoplasms1 medicine

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.

2 medicines meet Open Targets' target-level approved-medicine definition; the 1 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

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.

regorafenib
ApprovedInhibitor

Tyrosine-protein kinase FRK inhibitor

Indicated for Colorectal Neoplasms, Neoplasms

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

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 FRK

Gene-level evidence surfaced through the gene FRK that 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.

Precursor Cell Lymphoblastic Leukemia-Lymphoma
0.67Moderately supported

Clinical evidence dominant · Open Targets 0.54

Neoplasms
0.61Moderately supported

Clinical evidence dominant · Open Targets 0.49

Gout
0.61Moderately supported

Genetic evidence dominant · Open Targets 0.37

Colorectal Neoplasms
0.46Limited support

Clinical evidence dominant · Open Targets 0.37

Carcinoma, Hepatocellular
0.46Limited support

Clinical evidence dominant · Open Targets 0.37

View evidence synthesis (5)
Precursor Cell Lymphoblastic Leukemia-LymphomaModerately supported
0.67
agreement 0.520.82
Clinical99%Literature1%

Open Targets aggregate 0.54 · 2 independent evidence families

NeoplasmsModerately 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

Colorectal NeoplasmsLimited support
0.46
agreement 0.300.61
Clinical100%Literature0%

Open Targets aggregate 0.37 · 2 independent evidence families

Carcinoma, HepatocellularLimited support
0.46
agreement 0.300.61
Clinical97%Literature3%

Open Targets aggregate 0.37 · 2 independent evidence families

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
Precursor Cell Lymphoblastic Leukemia-Lymphoma0.54
Neoplasms0.49
Gout0.37
Colorectal Neoplasms0.37
Carcinoma, Hepatocellular0.37

Drug development

6 compounds recorded · 2 approved · 4 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 (6)
ILORASERTIBPhase 2
REGORAFENIBApproval
TG100-801Phase 2
DASATINIB ANHYDROUSApproval
ENMD-981693Phase 2
XL-228Phase 1

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 High-Quality Ligand support this modality.

AntibodiesEmerging

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

Protein degradersEmerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (6)
SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

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)

ClinicalTrials.gov via the drug-target graph.

What's happening now

9

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. Trial status changed2026-08-12

    A Phase II Study Using Regorafenib as Second or Third Line Therapy in Metastatic Medullary Thyroid Cancer

    Status changed to Completed · ClinicalTrials.gov · via regorafenib

  2. Trial status changed2026-07-21

    A Randomized Phase II, Placebo-controlled, Multicenter Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas

    Status changed to Completed · ClinicalTrials.gov · via regorafenib

  3. Trial results posted2026-07-20

    Neoadjuvant Regorafenib Plus Durvalumab (MEDI4736) in Patients With High-Risk Hepatocellular Carcinoma

    Results posted · ClinicalTrials.gov · via regorafenib

  4. 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

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

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

  6. 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

  7. 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

  8. 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

  9. 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.