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Protein / target

Tyrosine-protein kinase HCK

Encoded byHCKP08631Homo sapiensSwiss-Prot
UniProt: P08631Ensembl: ENSG00000101336HGNC: HGNC:4840NCBI Gene: 3055
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Non-membrane spanning protein tyrosine kinase

Strongest disease association

Hypertension

Via encoding gene HCK · Genetic evidence · score 0.62

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 found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and prolifera…

View complete UniProt function annotation

Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS

Subcellular location

LysosomeMembraneCell projection, podosome membraneCytoplasm, cytosolCell membraneMembrane, caveolaCell junction, focal adhesionCytoplasm, cytoskeletonGolgi apparatusCytoplasmic vesicleNucleusCytoplasmic vesicle, secretory vesicle
Domains and Gene Ontology detail (47)

Domains & features

SH3SH2Protein kinase

Gene Ontology

  • Ccaveola
  • Ccell projection
  • Ccytoplasmic side of plasma membrane
  • Ccytoskeleton
  • Ccytosol
  • Cfocal adhesion
  • CGolgi apparatus
  • Clysosome
  • Cnucleus
  • Cplasma membrane
  • Ctransport vesicle
  • FATP binding

526 aa · 60 kDa · 4 isoforms

Biological roles

Reactome v97

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

Cell proliferation & survivalUniProt · GOReceptor tyrosine kinase signallingGOImmune signallingUniProt · GOCell adhesionUniProt · GO
View supporting evidence

Cell proliferation & survival

  • ·Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals…
  • ·positive regulation of cell population proliferation

Receptor tyrosine kinase signalling

  • ·cell surface receptor protein tyrosine kinase signaling pathway

Immune signalling

  • ·Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals…
  • ·cytokine-mediated signaling pathway
  • ·inflammatory response
  • ·innate immune response-activating signaling pathway

Cell adhesion

  • ·Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals…
  • ·Cell junction, focal adhesion
  • ·cell adhesion
View underlying pathways (9)
Nef and signal transduction
FCGR activation
Regulation of signaling by CBL
FCGR3A-mediated IL10 synthesis
FCGR3A-mediated phagocytosis
Signaling by CSF3 (G-CSF)
Signaling by CSF1 (M-CSF) in myeloid cells
Inactivation of CSF3 (G-CSF) signaling
FLT3 signaling through SRC family kinases

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.

LYNELMO1PTPRCFCGR1ASHC1FCGR2APTK2FCGR3AITKFCGR3BHCK

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

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.

bosutinib
ApprovedInhibitor

Tyrosine-protein kinase HCK inhibitor

Direct interaction with this protein · 1 of 4 recorded protein targets

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 HCK

Gene-level evidence surfaced through the gene HCKthat 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.

chronic myelogenous leukemia, BCR-ABL1 positive
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.59

Precursor Cell Lymphoblastic Leukemia-Lymphoma
0.68Moderately supported

Clinical evidence dominant · Open Targets 0.55

Neoplasms
0.63Moderately supported

Clinical evidence dominant · Open Targets 0.49

Hypertension
0.62Moderately supported

Genetic evidence dominant · Open Targets 0.38

Essential Hypertension
0.62Moderately supported

Genetic evidence dominant · Open Targets 0.38

View evidence synthesis (5)
chronic myelogenous leukemia, BCR-ABL1 positiveModerately supported
0.72
agreement 0.59–0.86
Clinical96%Literature3%RNA expression1%

Open Targets aggregate 0.59 · 3 independent evidence families

Precursor Cell Lymphoblastic Leukemia-LymphomaModerately supported
0.68
agreement 0.52–0.83
Clinical97%Literature4%

Open Targets aggregate 0.55 · 2 independent evidence families

NeoplasmsModerately supported
0.63
agreement 0.47–0.78
Clinical84%Literature17%

Open Targets aggregate 0.49 · 2 independent evidence families

HypertensionModerately supported
0.62
agreement 0.48–0.76
Genetic99%Literature1%

Open Targets aggregate 0.38 · 2 independent evidence families

Essential HypertensionModerately supported
0.62
agreement 0.50–0.74
Genetic100%

Open Targets aggregate 0.38 · 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 per-type scores above show the calculation.

Show all associations
chronic myelogenous leukemia, BCR-ABL1 positive0.59
Precursor Cell Lymphoblastic Leukemia-Lymphoma0.55
Neoplasms0.49
Leishmaniasis, Cutaneous0.46
Breast Neoplasms0.43
Neurodegenerative Diseases0.42
Autoinflammation with pulmonary and cutaneous vasculitis0.40
Hypertension0.38
Essential Hypertension0.38

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: these count different sets and are not a subset relation.

View all recorded compounds (6)
DASATINIB ANHYDROUSApproval
BOSUTINIBApproval
ILORASERTIBPhase 2
ENMD-981693Phase 2
TG100-801Phase 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 molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Emerging

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

Protein degraders — Emerging

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

View underlying tractability evidence (12)
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 · UniProt UbiquitinationPR · Database UbiquitinationPR · 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.

An Open Label, Multi-center Asciminib Roll-over Study to Assess Long-term Safety in Patients Who Have Completed a Novartis Sponsored Asciminib Study and Are Judged by the Investigator to Benefit From Continued TreatmentPHASE4

RECRUITING · via bosutinib · NCT04877522

This is a Global, Multi-center, Open-label Randomized and Registrational Phase 3 Study of Olverembatinib (HQP1351) in Patients With Chronic Phase Chronic Myeloid LeukemiaPHASE3

RECRUITING · via bosutinib · NCT06423911

A Phase III, Multi-center, Open-label, Randomized Study of Oral Asciminib Versus Investigator Selected TKI in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic PhasePHASE3

ACTIVE_NOT_RECRUITING · via bosutinib · NCT04971226

A Phase I/II Study of Bosutinib in Pediatric Patients With Newly Diagnosed Chronic Phase or Resistant/Intolerant Ph + Chronic Myeloid Leukemia", Study ITCC-054/COG-AAML1921PHASE1/PHASE2

ACTIVE_NOT_RECRUITING · via bosutinib · NCT04258943

View all trials (26)
A Randomized Phase II Study of Ruxolitinib (NSC-752295) in Combination With BCR-ABL Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia (CML) Patients With Molecular Evidence of DiseasePHASE2

ACTIVE_NOT_RECRUITING · via bosutinib · NCT03654768

Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR): A Phase II Basket TrialPHASE2

RECRUITING · via bosutinib · NCT03297606

A PHASE 4 SAFETY AND EFFICACY STUDY OF BOSUTINIB (BOSULIF (REGISTERED)) IN PATIENTS WITH PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA PREVIOUSLY TREATED WITH ONE OR MORE TYROSINE KINASE INHIBITORSPHASE4

TERMINATED · via bosutinib · NCT02228382

A Phase 3, Multi-center, Open-label, Randomized Study of Oral ABL001 Versus Bosutinib in Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated With 2 or More Tyrosine Kinase InhibitorsPHASE3

COMPLETED · via bosutinib · NCT03106779

A MULTICENTER PHASE 3 RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB VERSUS IMATINIB IN ADULT PATIENTS WITH NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOGENOUS LEUKEMIAPHASE3

COMPLETED · via bosutinib · NCT02130557

A PHASE 3 RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB VERSUS IMATINIB IN SUBJECTS WITH NEWLY DIAGNOSED CHRONIC PHASE PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOGENOUS LEUKEMIAPHASE3

COMPLETED · via bosutinib · NCT00574873

Multicenter, Open-label, Phase Ib/II Trial to Evaluate Safety and Efficacy for the Combination of Bosutinib Plus Atezolizumab in Newly Diagnosed Chronic Myeloid Leukemia PatientsPHASE1/PHASE2

TERMINATED · via bosutinib · NCT04793399

Prospective Non-randomized Stratified Study of REduction And DIscontinuation Treatment of TKI (Imatinib, Nilotinib, Dasatinib and Bosutinib) in Adults With Ph+ Chronic Myeloid Leukemia With Stable Deep Molecular ResponsePHASE2

UNKNOWN · via bosutinib · NCT04578847

A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies (DLB)PHASE2

COMPLETED · via bosutinib · NCT03888222

A Study of Efficacy and Safety of Long-acting Low Dose Ropeginterferon in Patients With Chronic Myeloid Leukemia Treated With Bosutinib From Diagnosis: a Randomized Prospective TrialPHASE2

COMPLETED · via bosutinib · NCT03831776

Phase 1/2 Study of Bosutinib in Patients With Amyotrophic Lateral Sclerosis (ALS)PHASE1/PHASE2

UNKNOWN · via bosutinib · NCT04744532

A PHASE 2, OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE EFFICACY AND SAFETY OF BOSUTINIB MONOTHERAPY IN JAPANESE ADULT PATIENTS WITH NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOGENOUS LEUKEMIAPHASE2

COMPLETED · via bosutinib · NCT03128411

Bosutinib Efficacy, Safety, Tolerability (BEST) Study in Elderly Chronic Myeloid Leukemia Patients Failing Front-line Treatment With Other Tyrosine Kinase InhibitorsPHASE2

COMPLETED · via bosutinib · NCT02810990

An Open-Label Phase II Dose Optimization Study of Bosutinib at a Starting Dose of 300 Mg Daily for Adult Patients With Chronic Myeloid Leukemia (CML) in Chronic Phase Post Frontline TKI FailurePHASE2

TERMINATED · via bosutinib · NCT02906696

Allogeneic Haematopoietic Stem Cell Transplantation From a Matched Donor in Patients With Chronic Myeloid Leukemia Failing to Gain Normal Hemopoiesis Under TKIs TherapyPHASE2

COMPLETED · via bosutinib · NCT02638467

Single Nucleotide Polymorphism Association With Response and Toxic Effects in Patients With Ph+ CP-CML Treated With Bosutinib After Relapse to Previous TreatmentPHASE2

COMPLETED · via bosutinib · NCT02445742

A Phase I/II Study of Bosutinib in Combination With Inotuzumab Ozogamicin in CD22-Positive Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia Lymphoid Blast PhasePHASE1/PHASE2

COMPLETED · via bosutinib · NCT02311998

The Life After Stopping Tyrosine Kinase Inhibitors Study (The LAST Study)PHASE2

COMPLETED · via bosutinib · NCT02269267

An Open Label, Phase 2 Trial of Orally Administered Bosutinib (SKI-606) in Adult Patients With Recurrent Glioblastoma (GBM)PHASE2

COMPLETED · via bosutinib · NCT01331291

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Of The Safety, Clinical Activity And Pharmacokinetics Of Bosutinib (PF-05208763) Versus Placebo In Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)PHASE2

COMPLETED · via bosutinib · NCT01233869

A Phase 1/2, Open-Label Study Of Bosutinib Administered In Combination With Capecitabine In Subjects With Solid Tumor And ErbB2 Negative Locally Advanced Or Metastatic Breast CancerPHASE1/PHASE2

TERMINATED · via bosutinib · NCT00959946

A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB ADMINISTERED IN COMBINATION WITH LETROZOLE VS. LETROZOLE ALONE AS FIRST LINE THERAPY IN POST-MENOPAUSAL WOMEN WITH LOCALLY ADVANCED OR METASTATIC ER+/PR+/HER2- BREAST CANCER.PHASE2

TERMINATED · via bosutinib · NCT00880009

A Phase 2, Randomized, Open-Label Study Of Bosutinib Administered In Combination With Exemestane Versus Exemestane Alone As Second Line Therapy In Postmenopausal Women With Locally Advanced Or Metastatic ER+/PgR+/ErbB2- Breast CancerPHASE2

TERMINATED · via bosutinib · NCT00793546

A Phase 1/2 Study Of Bosutinib (Ski-606) In Philadelphia Chromosome Positive LeukemiasPHASE2

COMPLETED · via bosutinib · NCT00261846

A PHASE 1, RANDOMIZED, OPEN-LABEL, 3-PERIOD, 4-SEQUENCE, CROSSOVER, SINGLE-DOSE STUDY TO COMPARE THE BIOAVAILABILITY OF ORALLY ADMINISTERED BOSUTINIB CAPSULES AND TO ESTIMATE THE EFFECT OF FOOD ON BOSUTINIB CAPSULEPHASE1

COMPLETED · via bosutinib · NCT05032690

A PHASE 1, OPEN-LABEL, RANDOMIZED, 3-PERIOD, 6-SEQUENCE, CROSSOVER STUDY TO EVALUATE THE BIOAVAILABILITY OF BOSUTINIB ADMINISTERED AS CAPSULE CONTENTS MIXED WITH APPLESAUCE OR YOGURT RELATIVE TO INTACT CAPSULES IN HEALTHY PARTICIPANTS UNDER FED CONDITIONPHASE1

COMPLETED · via bosutinib · NCT04916769

ClinicalTrials.gov via the drug-target graph.

What's happening now

4

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 approval2026-06-12

    Approval: BOSUTINIB (ANDA209624)

    fda · regulatory · fda · via bosutinib

  2. Regulatory approval2025-05-23

    Approval: BOSUTINIB (ANDA209543)

    fda · regulatory · fda · via bosutinib

  3. New publication2020-03-03
    European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia.

    Leukemia · 2020 · 1,035 citations · Europe PMC · via bosutinib

  4. Regulatory approval2013-03-27

    Approval: Bosulif (EMA)

    ema · regulatory · ema · via bosutinib

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.