Protein / target

Tyrosine-protein kinase HCK

HCKP08631Homo sapiensSwiss-Prot
UniProt: P08631Ensembl: ENSG00000101336HGNC: HGNC:4840NCBI Gene: 3055
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

Primary system

Immune system

Strongest disease association

hypertensive disorder

Genetic evidence · score 0.62

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 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.

Kinase signallingUniProt · GOImmune signallingUniProt · GOCell adhesionUniProt · GOTranscriptional regulationUniProtApoptosis & cell deathGOMuscle contractionGO
View supporting evidence

Kinase signalling

  • ·Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals…
  • ·non-membrane spanning protein tyrosine kinase activity
  • ·protein tyrosine kinase activity
  • ·peptidyl-tyrosine phosphorylation

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

Transcriptional regulation

  • ·Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals…

Apoptosis & cell death

  • ·negative regulation of apoptotic process

Muscle contraction

  • ·positive regulation of actin filament polymerization
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

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.

bosutinib
ApprovedInhibitor

Tyrosine-protein kinase HCK inhibitor

Appears in clinical studies involving breast cancer, neoplasm, chronic myelogenous leukemia, BCR-ABL1 positive, chronic myelogenous leukemia, BCR-ABL1 positive

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

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.

hypertensive disorder0.62

Genetic · overall 0.38

essential hypertension0.62

Genetic · overall 0.38

autoinflammation with pulmonary and cutaneous vasculitis0.50

Genetic · overall 0.40

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 0.59

acute lymphoblastic leukemia0.89

Clinical · overall 0.55

neoplasm0.77

Clinical · overall 0.49

breast cancer0.68

Clinical · overall 0.43

lymphoid leukemia0.67

Clinical · overall 0.41

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

cutaneous leishmaniasis0.46

Pathway

neurodegenerative disease0.42

Pathway

Show all associations
chronic myelogenous leukemia, BCR-ABL1 positive0.59
acute lymphoblastic leukemia0.55
neoplasm0.49
cutaneous leishmaniasis0.46
breast cancer0.43
neurodegenerative disease0.42
lymphoid leukemia0.41
autoinflammation with pulmonary and cutaneous vasculitis0.40
hypertensive disorder0.38
essential hypertension0.38

Open Targets ranks 731 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

DASATINIB ANHYDROUSApproval

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

BOSUTINIBApproval

breast cancer · neoplasm · chronic myelogenous leukemia, BCR-ABL1 positive

ILORASERTIBPhase 2

juvenile myelomonocytic leukemia · acute myeloid leukemia · myelodysplastic syndrome

ENMD-981693Phase 2

colorectal carcinoma · breast carcinoma · exocrine pancreatic carcinoma

TG100-801Phase 2

macular degeneration · age-related macular degeneration

XL-228Phase 1

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

Tractability

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

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.

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

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

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 Study to Examine the Potential Effect of Rifampin on the Pharmacokinetics of Bosutinib When Administered Concomitantly to Healthy SubjectsPHASE1

COMPLETED · via bosutinib · NCT00725426

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

COMPLETED · via bosutinib · NCT00261846

A Study to Examine The Potential Effect Of Lansoprazole On The Pharmacokinetics Of Bosutinib When Administered Concomitantly To Healthy SubjectsPHASE1

COMPLETED · via bosutinib · NCT00952913

Show remaining trials (24)
An Open-Label, Randomized, Single-Dose, 2-Period Crossover Study to Determine the Effect of a High-Fat Meal on the Relative Bioavailability and Pharmacokinetics of a Single Dose of Bosutinib Administered Orally to Healthy SubjectsPHASE1

COMPLETED · via bosutinib · NCT00721474

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

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

COMPLETED · via bosutinib · NCT02269267

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

An Open-label, Randomized, 2-period Crossover Study To Evaluate Absolute Bioavailability Of Bosutinib In Healthy SubjectsPHASE1

COMPLETED · via bosutinib · NCT02192294

Open Label Study for the Use of Tyrosine Kinase Inhibitors for Treatment of Cognitive Decline Due to Degenerative DementiasPHASE1

UNKNOWN · via bosutinib · NCT02921477

Alternating or Combined Therapy With Axitinib and Bosutinib for Patients With Chronic Myeloid Leukemia in Chronic, Accelerated, or Blastic PhasesPHASE1

TERMINATED · via bosutinib · NCT02782403

AN OPEN-LABEL BOSUTINIB TREATMENT EXTENSION STUDY FOR SUBJECTS WITH CHRONIC MYELOID LEUKEMIA (CML) WHO HAVE PREVIOUSLY PARTICIPATED IN BOSUTINIB STUDIES B1871006 OR B1871008NA

COMPLETED · via bosutinib · NCT01903733

A Phase I Trial of Palbociclib and Bosutinib With Fulvestrant in Patients With Metastatic Hormone Receptor Positive and HER2 Negative (HR+ HER2-) Breast Cancer Refractory to an Aromatase Inhibitor and a CDK4/6 Inhibitor (ASPIRE - WI231696)PHASE1

COMPLETED · via bosutinib · NCT03854903

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

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

An Open-Label, Randomized, 2-Period Crossover Study To Evaluate The Effect Of A Single Oral Dose Of Bosutinib On The Pharmacokinetics Of Dabigatran Etexilate Mesylate Administered Orally To Healthy SubjectsPHASE1

COMPLETED · via bosutinib · NCT02102633

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

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

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

Phase I Dose-Escalation Study Of Oral SKI-606 In Subjects With Advanced Malignant Solid TumorsPHASE1

COMPLETED · via bosutinib · NCT00195260

An Open-Label, Single-Dose, Parallel-Group Study of the Pharmacokinetics and Safety of Bosutinib in Subjects With Chronic Hepatic Impairment and in Matched Healthy AdultsPHASE1

COMPLETED · via bosutinib · NCT00759837

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, 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 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

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

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

An Open-Label, Single-Dose, Parallel-Group Study Of The Pharmacokinetics And Safety Of Bosutinib In Subjects With Renal Impairment And Matched Healthy AdultsPHASE1

COMPLETED · via bosutinib · NCT01233882

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

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
0.72
agreement 0.59–0.86
Clinical96%Literature3%RNA expression1%

Open Targets aggregate 0.59 · 3 independent evidence families

acute lymphoblastic leukemiaModerately supported
0.68
agreement 0.52–0.83
Clinical97%Literature4%

Open Targets aggregate 0.55 · 2 independent evidence families

neoplasmModerately supported
0.63
agreement 0.47–0.78
Clinical84%Literature17%

Open Targets aggregate 0.49 · 2 independent evidence families

hypertensive disorderModerately 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

4

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. 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.