Protein / target

Discoidin domain-containing receptor 2

DDR2Q16832Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Transmembrane receptor protein tyrosine kinase activity

Primary system

Musculoskeletal system

Strongest disease association

spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome

Genetic evidence · score 0.86

Therapeutic maturity

Clinically validated target

1 approved medicine against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

1 approved

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

Tyrosine kinase involved in the regulation of tissues remodeling (PubMed:30449416). It functions as a cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing

Subcellular location

Cell membrane
Domains and Gene Ontology detail (45)

Domains & features

F5/8 type CProtein kinase

Gene Ontology

  • Capical plasma membrane
  • Cfocal adhesion
  • Cplasma membrane
  • Creceptor complex
  • FATP binding
  • Fcollagen binding
  • Fprotein tyrosine kinase collagen receptor activity
  • Ftransmembrane receptor protein tyrosine kinase activity
  • Pbiomineral tissue development
  • Pcell adhesion
  • Pcell surface receptor protein tyrosine kinase signaling pathway
  • Pcellular response to angiotensin

855 aa · 97 kDa

Biological roles

Reactome v97

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

Cell adhesionUniProt · GOKinase signallingGOApoptosis & cell deathGOTranscriptional regulationUniProt
View supporting evidence

Cell adhesion

  • ·Tyrosine kinase involved in the regulation of tissues remodeling (PubMed:30449416). It f…
  • ·cell adhesion
  • ·positive regulation of extracellular matrix disassembly
  • ·regulation of extracellular matrix disassembly

Kinase signalling

  • ·transmembrane receptor protein tyrosine kinase activity
  • ·peptidyl-tyrosine phosphorylation
  • ·positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  • ·positive regulation of protein kinase activity

Apoptosis & cell death

  • ·negative regulation of apoptotic process
  • ·negative regulation of hydrogen peroxide-mediated programmed cell death

Transcriptional regulation

  • ·Tyrosine kinase involved in the regulation of tissues remodeling (PubMed:30449416). It f…
View underlying pathways (1)

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.

COL1A1COL3A1COL11A1COL5A1ITGA2SHC1EML4COL4A1VWFDDR1DDR2

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

Discoidin domain-containing receptor 2 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.

spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome0.86

Genetic · overall 0.78

Spondyloepimetaphyseal dysplasia - short limb - abnormal calcification0.83

Genetic · overall 0.75

Abnormality of the skeletal system0.71

Genetic · overall 0.43

Dupuytren Contracture0.70

Genetic · overall 0.42

Warburg-Cinotti syndrome0.65

Genetic · overall 0.57

Highest-confidence therapeutic associations

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

colorectal cancer0.94

Clinical · overall 0.58

metastatic colorectal cancer0.67

Clinical · overall 0.41

neoplasm0.62

Clinical · overall 0.41

hepatocellular carcinoma0.60

Clinical · overall 0.45

gastrointestinal stromal tumor0.59

Clinical · overall 0.41

Show all associations
spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome0.78
Spondyloepimetaphyseal dysplasia - short limb - abnormal calcification0.75
colorectal cancer0.58
Warburg-Cinotti syndrome0.57
hepatocellular carcinoma0.45
Abnormality of the skeletal system0.43
Dupuytren Contracture0.42
neoplasm0.41
metastatic colorectal cancer0.41
gastrointestinal stromal tumor0.41

Open Targets ranks 1,017 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 · 1 total

REGORAFENIBApproval

colorectal cancer · metastatic colorectal cancer · colorectal neoplasm

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · LiteraturePR · 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.

spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndromeWell supported
0.88
agreement 0.761.00
Genetic86%Animal model14%Genetic literaturedup

Open Targets aggregate 0.78 · 2 independent evidence families · 1 not counted as duplicate

Spondyloepimetaphyseal dysplasia - short limb - abnormal calcificationWell supported
0.86
agreement 0.730.98
Genetic86%Animal model14%Genetic literaturedup

Open Targets aggregate 0.75 · 2 independent evidence families · 1 not counted as duplicate

colorectal cancerModerately supported
0.72
agreement 0.580.85
Clinical93%RNA expression5%Literature3%

Open Targets aggregate 0.58 · 3 independent evidence families

Abnormality of the skeletal systemModerately supported
0.71
agreement 0.590.83
Genetic100%

Open Targets aggregate 0.43 · 1 independent evidence family

Dupuytren ContractureModerately supported
0.70
agreement 0.580.82
Genetic100%

Open Targets aggregate 0.42 · 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.