DDR2

Summary

DDR2 (discoidin domain receptor tyrosine kinase 2, HGNC:2731) is a protein-coding gene on chromosome 1q23.3, encoding Discoidin domain-containing receptor 2 (Q16832). Tyrosine kinase involved in the regulation of tissues remodeling. In precision oncology, DDR2 S768R confers sensitivity to Erlotinib + Dasatinib in Lung Non-small Cell Carcinoma (CIViC Level C); 6 further curated variant–drug associations are listed below.

This gene encodes a member of the discoidin domain receptor subclass of the receptor tyrosine kinase (RTKs) protein family. RTKs play a key role in the communication of cells with their microenvironment. The encoded protein is a collagen-induced receptor that activates signal transduction pathways involved in cell adhesion, proliferation, and extracellular matrix remodeling. This protein is expressed in numerous cell types and may alos be involved in wound repair and regulate tumor growth and invasiveness. Mutations in this gene are the cause of short limb-hand type spondylometaepiphyseal dysplasia.

Source: NCBI Gene 4921 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 25
• Clinical variants (ClinVar): 614 total — 20 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 127
• Druggable target: yes — 59 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 7 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_006182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2731
Approved symbol	DDR2
Name	discoidin domain receptor tyrosine kinase 2
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	TKT
Ensembl gene	ENSG00000162733
Ensembl biotype	protein_coding
OMIM	191311
Entrez	4921

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 23 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000367921, ENST00000367922, ENST00000415555, ENST00000433757, ENST00000446985, ENST00000458105, ENST00000671979, ENST00000672207, ENST00000673239, ENST00000877159, ENST00000877160, ENST00000877161, ENST00000877162, ENST00000877163, ENST00000877164, ENST00000877165, ENST00000877166, ENST00000877167, ENST00000877168, ENST00000877169, ENST00000877170, ENST00000877171, ENST00000877172, ENST00000966492, ENST00000966493, ENST00000966494, ENST00000966495

RefSeq mRNA: 4 — MANE Select: NM_006182 NM_001014796, NM_001354982, NM_001354983, NM_006182

CCDS: CCDS1241

Canonical transcript exons

ENST00000367921 — 18 exons

Exon	Start	End
ENSE00000983497	162719037	162719145
ENSE00001068052	162761211	162761454
ENSE00001165607	162776136	162776370
ENSE00001165614	162775652	162775843
ENSE00001165621	162773469	162773596
ENSE00001165626	162772024	162772247
ENSE00001165634	162770302	162770512
ENSE00001165641	162767229	162767359
ENSE00001165652	162766001	162766063
ENSE00001165686	162754624	162754855
ENSE00001165692	162753095	162753197
ENSE00001165699	162655211	162655374
ENSE00001820621	162632464	162632631
ENSE00001945551	162780112	162787405
ENSE00002333595	162759796	162759979
ENSE00002367513	162778580	162778729
ENSE00002414929	162755664	162755769
ENSE00002705009	162755156	162755303

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 99.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.3243 / max 731.2485, expressed in 1153 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6317	23.0687	1090
6316	4.5223	985
6319	2.9355	679
6318	0.5133	277
6311	0.3822	236
6312	0.3630	211
6313	0.3347	184
201796	0.1127	43
6315	0.0524	21
6314	0.0396	14

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	99.15	gold quality
tendon of biceps brachii	UBERON:0008188	98.62	gold quality
vena cava	UBERON:0004087	98.54	gold quality
synovial joint	UBERON:0002217	97.37	gold quality
calcaneal tendon	UBERON:0003701	97.29	gold quality
tendon	UBERON:0000043	97.05	gold quality
caput epididymis	UBERON:0004358	97.03	gold quality
cartilage tissue	UBERON:0002418	97.02	gold quality
tibia	UBERON:0000979	97.00	gold quality
buccal mucosa cell	CL:0002336	96.83	gold quality
pericardium	UBERON:0002407	96.80	gold quality
urethra	UBERON:0000057	96.69	gold quality
skin of hip	UBERON:0001554	96.62	gold quality
superficial temporal artery	UBERON:0001614	96.48	gold quality
colonic epithelium	UBERON:0000397	96.39	gold quality
saphenous vein	UBERON:0007318	96.28	gold quality
lower lobe of lung	UBERON:0008949	96.05	gold quality
parietal pleura	UBERON:0002400	96.02	gold quality
left adrenal gland	UBERON:0001234	95.84	gold quality
adrenal cortex	UBERON:0001235	95.69	gold quality
corpus epididymis	UBERON:0004359	95.67	gold quality
right adrenal gland	UBERON:0001233	95.66	gold quality
left adrenal gland cortex	UBERON:0035825	95.52	gold quality
right adrenal gland cortex	UBERON:0035827	95.43	gold quality
mammary duct	UBERON:0001765	95.32	gold quality
adrenal gland	UBERON:0002369	95.29	gold quality
stromal cell of endometrium	CL:0002255	95.17	gold quality
layer of synovial tissue	UBERON:0007616	94.85	gold quality
pigmented layer of retina	UBERON:0001782	94.57	gold quality
trabecular bone tissue	UBERON:0002483	94.48	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-11	yes	317.26
E-GEOD-98556	yes	280.25
E-CURD-46	yes	20.56
E-MTAB-5061	yes	10.96
E-GEOD-83139	yes	7.42
E-ENAD-27	yes	6.36
E-CURD-112	yes	5.82
E-MTAB-7249	yes	3.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, CEBPB, CEBPG, MAX, MYC

miRNA regulators (miRDB)

29 targeting DDR2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-198	98.70	67.32	920
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-3162-5P	95.67	67.53	794
HSA-MIR-3622B-5P	94.62	64.58	835

Literature-anchored findings (GeneRIF, showing 40)

• gene expression analysis with DDR2 overexpression, using microarrays specific for human and mouse genes coding for extracellular matrix proteins or ECM-interacting factors (PMID:12935821)
• DDR1 and DDR2 have roles in the regulation of collagen turnover mediated by SMCs in obstructive diseases of blood vessels and the lung (PMID:15111304)
• Results describe a site-specific interaction of discoidin domain receptor 2 with collagen II and gives novel insight into the nature of the interaction of collagen II with matrix receptors. (PMID:15544808)
• DDR2 2 mediates tumor cell cycle arrest induced by fibrillar collagen (PMID:16186104)
• DDR2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of DDR2 cytosolic domain-Shc signaling complexes. (PMID:16186108)
• the triple-helical region of collagen X contains a specific DDR2 binding site that is capable of receptor activation (PMID:16806867)
• All these findings suggested that the fused expressed His-DR inhibited the activity of natural DDR2, and relevant MMP-1 and MMP-2 expression in synoviocytes and NIH3T3 cells provoked by collagen II. (PMID:16967187)
• altered expression of DDR1 may contribute to malignant progression of non-small cell lung carcinoma (PMID:17299390)
• This study provides a molecular basis for the collagen-binding mode of the DDR2-DS domain. (PMID:17703188)
• Overexpression of DDR2 is associated with papillary thyroid carcinomas (PMID:17786355)
• the perpetuation of DDR-2 expression and activation can be seen as a vicious circle that ultimately leads to cartilage destruction in osteoarthritis (PMID:17968949)
• DDR2 activation may be effected by single triple-helices rather than fibrillar collagen (PMID:18201965)
• There are three missense mutations c.2254 C > T [R752C], c. 2177 T > G [I726R], c.2138C > T [T713I] and one splice site mutation [IVS17+1g > a] in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene. (PMID:19110212)
• DDR2-mediated MMP-13 induction by collagen matrix in synovial fibroblasts of RA contributed to articular cartilage destruction (PMID:19415460)
• Spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcifications can result from at least two different loss-of-function mechanisms: defects in DDR2 targeting to the plasma membrane or the loss of its ligand-binding activity. (PMID:20223752)
• The stimulation of p38 MAPK by DDR2 was required for DDR2-induced activation of Runx2 and OCN promoters. (PMID:20564243)
• Collagen I induces discoidin domain receptor (DDR) 1 expression through DDR2 and a JAK2-ERK1/2-mediated mechanism in primary human lung fibroblasts. (PMID:21335558)
• Discoidin domain receptor 2 is a critical regulator of epithelial-mesenchymal transition (PMID:21477649)
• DDR2 promotes A375 melanoma metastasis to the liver and the underlying mechanism implicates regulation of metalloproteinase release, cell growth and chemotactic invasion of the host tissue. (PMID:21701781)
• gain-of-function mutations in DDR2 are important oncogenic events in squamous cell lung cancer. (PMID:22328973)
• DDR2-microRNA-196a pathway may be a previously unreported negative feedback system, and its impairment may be involved in the pathogenesis of systemic sclerosis. (PMID:22832484)
• DDR2 is required for normal fibroblast spreading and migration independent of adhesion ligand and collagen activation of DDR2 tyrosine kinase. (PMID:23131558)
• DDR2 regulates directionality through its ability to increase secretion of metalloproteinases and local generation of collagen-derived chemotactic peptide gradients. (PMID:23233663)
• DDR2 is an independent favorable predictor for prognosis in human breast cancer. (PMID:23307244)
• Mutations in the DDR2 gene were recently identified in squamous cell lung cancer through a sequencing screen of 201 genes with a potential role in human cancer (including the entire tyrosine kinome). (PMID:23401445)
• DDR2 functioning is required for the membrane dynamics to control the mechanical attachment of fibroblasts to the 3D collagen matrices in an integrin-independent manner. (PMID:23546533)
• DDR2 maintains SNAIL1 level and activity in tumour cells that have undergone epithelial-mesenchymal transition (EMT), thereby facilitating continued tumour cell invasion through collagen-I-rich extracellular matrices by sustaining the EMT phenotype. (PMID:23644467)
• SHP-2 is a key signalling node downstream of the DDR2 receptor in lung cancer. (PMID:23822953)
• regulation of DDRs by glucose (PMID:24018687)
• Loss of DDR2 suppresses tumor angiogenesis and tumor metastasis to the lung. (PMID:24293323)
• Data show two distinct mechanisms of acquired resistance: acquisition of the T654I gatekeeper mutation in discoidin domain receptor tyrosine kinase 2 (DDR2) and loss of neurofibromin 1 (NF1). (PMID:24296828)
• In this review we highlight the mechanisms whereby DDRs(DDR1 and DDR2) regulate two important processes, namely inflammation and tissue fibrosis. (PMID:24361528)
• Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements. (PMID:24505276)
• DDR2 plays an important role in head and neck squamous cell carcinoma metastasis, and might be a promising target for future therapies in this type of cancer. (PMID:24556606)
• Cbl-b, by promoting the ubiquitination and degradation of DDR2, functions as a negative regulator in the DDR2 signaling pathway. (PMID:24631539)
• High DDR2 protein expression is associated with recurrence in ameloblastomas. (PMID:24723326)
• A novel missense deletion mutation in DDR2 causing spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcifications (SMED-SL) results in defective intra-cellular trafficking. (PMID:24725993)
• DDR2 overexpression is associated with neoplasms. (PMID:24740739)
• DDR2 signaling regulates cell proliferation and extracellular matrix synthesis, which are key aspects of fibroblast contribution to tissue healing [review] (PMID:24781958)
• Discoidin domain receptor 2 facilitates prostate cancer bone metastasis via regulating parathyroid hormone-related protein. (PMID:24787381)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddr2b	ENSDARG00000058695
danio_rerio	ddr2a	ENSDARG00000100693
mus_musculus	Ddr2	ENSMUSG00000026674
rattus_norvegicus	Ddr2	ENSRNOG00000002881

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Discoidin domain-containing receptor 2 — Q16832 (reviewed: Q16832)

Alternative names: CD167 antigen-like family member B, Discoidin domain-containing receptor tyrosine kinase 2, Neurotrophic tyrosine kinase, receptor-related 3, Receptor protein-tyrosine kinase TKT, Tyrosine-protein kinase TYRO10

All UniProt accessions (3): A0A5F9ZI27, Q16832, Q5T244

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine kinase involved in the regulation of tissues remodeling. 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.

Subunit / interactions. Binds hydroxyproline-rich sequence motifs in fibrillar, glycosylated collagen, such as the GQOGVMGFO motif, where O stands for hydroxyproline. Interacts with SRC. Interacts (tyrosine phosphorylated) with SHC1.

Subcellular location. Cell membrane.

Tissue specificity. Detected in osteocytes, osteoblastic cells in subchondral bone, bone lining cells, tibia and cartilage (at protein level). Detected at high levels in heart and lung, and at low levels in brain, placenta, liver, skeletal muscle, pancreas, and kidney.

Post-translational modifications. N-glycosylated. Tyrosine phosphorylated in response to collagen binding. Phosphorylated by SRC; this is required for activation and subsequent autophosphorylation on additional tyrosine residues.

Disease relevance. Spondyloepimetaphyseal dysplasia, short limb-hand type (SEMD-SL) [MIM:271665] A bone disease characterized by short-limbed dwarfism, a narrow chest with pectus excavatum, brachydactyly in the hands and feet, a characteristic craniofacial appearance and premature calcifications. The radiological findings are distinctive and comprise short long bones throughout the skeleton with striking epiphyses that are stippled, flattened and fragmented and flared, irregular metaphyses. Platyspondyly in the spine with wide intervertebral spaces is observed and some vertebral bodies are pear-shaped with central humps, anterior protrusions and posterior scalloping. The disease is caused by variants affecting the gene represented in this entry. Warburg-Cinotti syndrome (WRCN) [MIM:618175] An autosomal dominant disease characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acro-osteolysis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Present in an inactive state in the absence of collagen binding and phosphorylation by SRC. Tyrosine phosphorylation enhances the affinity for ATP and the catalytic activity.

Induction. Up-regulated during osteoblast differentiation (in vitro). Up-regulated in cartilage from osteoarthritis patients.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

RefSeq proteins (4): NP_001014796, NP_001341911, NP_001341912, NP_006173* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000421	FA58C	Domain
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR002011	Tyr_kinase_rcpt_2_CS	Conserved_site
IPR008266	Tyr_kinase_AS	Active_site
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR020635	Tyr_kinase_cat_dom	Domain
IPR048525	DDR1-2_DS-like	Domain
IPR050122	RTK	Family

Pfam: PF00754, PF07714, PF21114

Enzyme classification (BRENDA):

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (82 total): strand 22, helix 17, sequence variant 11, glycosylation site 5, mutagenesis site 5, modified residue 4, turn 4, binding site 2, topological domain 2, disulfide bond 2, domain 2, signal peptide 1, chain 1, transmembrane region 1, sequence conflict 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2WUH	X-RAY DIFFRACTION	1.6
7AYM	X-RAY DIFFRACTION	2.12
7AZB	X-RAY DIFFRACTION	2.62
6FER	X-RAY DIFFRACTION	2.87
2Z4F	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16832-F1	76.57	0.41

Antibody-complex structures (SAbDab): 1 — 7AZB

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 710 (proton acceptor)

Ligand- & substrate-binding residues (2): 608; 569–577

Post-translational modifications (4): 471, 736, 740, 741

Disulfide bonds (2): 30–185, 73–177

Glycosylation sites (5): 121, 213, 261, 280, 372

Mutagenesis-validated functional residues (5):

Position	Phenotype
52	abolishes collagen binding.
608	abolishes kinase activity.
736	reduces autophosphorylation. abolishes phosphorylation by src; when associated with f-740 and f-741.
740	promotes autophosphorylation. abolishes phosphorylation by src; when associated with f-736 and f-741.
741	reduces autophosphorylation. abolishes phosphorylation by src; when associated with f-736 and f-740.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3000171	Non-integrin membrane-ECM interactions

MSigDB gene sets: 930 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_WOUND_HEALING, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_RESPONSE_TO_MUSCLE_STRETCH, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_NADPPLUS_METABOLIC_PROCESS, MODULE_64, GOBP_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION

GO Biological Process (38): ossification (GO:0001503), endochondral bone growth (GO:0003416), cell adhesion (GO:0007155), signal transduction (GO:0007165), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), regulation of extracellular matrix disassembly (GO:0010715), positive regulation of fibroblast migration (GO:0010763), positive regulation of neuron projection development (GO:0010976), peptidyl-tyrosine phosphorylation (GO:0018108), collagen fibril organization (GO:0030199), regulation of bone mineralization (GO:0030500), biomineral tissue development (GO:0031214), positive regulation of collagen biosynthetic process (GO:0032967), regulation of tissue remodeling (GO:0034103), chondrocyte proliferation (GO:0035988), response to muscle stretch (GO:0035994), collagen-activated tyrosine kinase receptor signaling pathway (GO:0038063), negative regulation of apoptotic process (GO:0043066), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of protein kinase activity (GO:0045860), protein autophosphorylation (GO:0046777), positive regulation of fibroblast proliferation (GO:0048146), obsolete positive regulation of DNA-binding transcription factor activity (GO:0051091), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to hypoxia (GO:0071456), cellular response to transforming growth factor beta stimulus (GO:0071560), positive regulation of extracellular matrix disassembly (GO:0090091), positive regulation of wound healing (GO:0090303), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), negative regulation of hydrogen peroxide-mediated programmed cell death (GO:1901299), cellular response to angiotensin (GO:1904385), positive regulation of vascular associated smooth muscle cell proliferation (GO:1904707), positive regulation of vascular associated smooth muscle cell migration (GO:1904754), positive regulation of hepatic stellate cell proliferation (GO:1904899), positive regulation of hepatic stellate cell activation (GO:2000491), protein phosphorylation (GO:0006468), positive regulation of cell population proliferation (GO:0008284)

GO Molecular Function (10): transmembrane receptor protein tyrosine kinase activity (GO:0004714), collagen binding (GO:0005518), ATP binding (GO:0005524), protein tyrosine kinase collagen receptor activity (GO:0038062), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (6): plasma membrane (GO:0005886), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), apical plasma membrane (GO:0016324), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
protein kinase activity	2
multicellular organismal process	1
bone growth	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
extracellular matrix disassembly	1
regulation of extracellular matrix organization	1
fibroblast migration	1
regulation of fibroblast migration	1
positive regulation of cell migration	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
protein phosphorylation	1
peptidyl-tyrosine modification	1
extracellular matrix organization	1
regulation of ossification	1
bone mineralization	1
regulation of biomineral tissue development	1
tissue development	1
animal organ development	1
positive regulation of biosynthetic process	1
positive regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1
tissue remodeling	1
regulation of multicellular organismal process	1
cell population proliferation	1
response to mechanical stimulus	1
cell surface receptor protein tyrosine kinase signaling pathway	1
collagen-activated signaling pathway	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
osteoblast differentiation	1
positive regulation of cell differentiation	1

Protein interactions and networks

STRING

1348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDR2	COL1A1	P02452	827
DDR2	COL3A1	P02461	793
DDR2	COL11A1	P12107	754
DDR2	COL5A1	P20908	723
DDR2	ITGA2	P17301	715
DDR2	EML4	Q9HC35	669
DDR2	VWF	P04275	645
DDR2	PIK3CA	P42336	640
DDR2	COL4A1	P02462	612
DDR2	KRAS	P01116	597
DDR2	NRAS	P01111	582
DDR2	COL2A1	P02458	574
DDR2	SHC1	P29353	558
DDR2	NTRK1	P04629	522
DDR2	EGFR	P00533	515

IntAct

56 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
DDR2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.640
DDR2	SHC1	psi-mi:“MI:0915”(physical association)	0.630
DDR2	DDR1	psi-mi:“MI:0915”(physical association)	0.620
DDR2	CDC37	psi-mi:“MI:0915”(physical association)	0.600
DDR2		psi-mi:“MI:0407”(direct interaction)	0.560
COL11A2	DDR2	psi-mi:“MI:0407”(direct interaction)	0.560
DDR2	COL11A2	psi-mi:“MI:0407”(direct interaction)	0.560
DDR2	NTRK3	psi-mi:“MI:0915”(physical association)	0.500
	DDR2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
APP	DDR2	psi-mi:“MI:0407”(direct interaction)	0.440
DDR2		psi-mi:“MI:0407”(direct interaction)	0.440
	DDR2	psi-mi:“MI:0915”(physical association)	0.400
SRC	DDR2	psi-mi:“MI:0915”(physical association)	0.400
CBLB	DDR2	psi-mi:“MI:0915”(physical association)	0.400
CHORDC1	SSR3	psi-mi:“MI:0914”(association)	0.350
GOLT1B		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
DDR2	Ptpn6	psi-mi:“MI:0914”(association)	0.350
DDR2	PLD2	psi-mi:“MI:0914”(association)	0.350
DDR1	TCAF2	psi-mi:“MI:0914”(association)	0.350
LRRC52	DYSF	psi-mi:“MI:0914”(association)	0.350
MICB	LGALS8	psi-mi:“MI:0914”(association)	0.350

BioGRID (171): CDH1 (Affinity Capture-Western), CDH2 (Affinity Capture-Western), DDR2 (Affinity Capture-MS), DDR2 (Affinity Capture-MS), DDR2 (Affinity Capture-MS), CBLB (Affinity Capture-Western), SHC1 (Two-hybrid), DDR2 (Affinity Capture-MS), DDR2 (Affinity Capture-MS), TK1 (Negative Genetic), PTP4A3 (Negative Genetic), TST (Negative Genetic), DDR2 (Negative Genetic), DMPK (Negative Genetic), PIK3CB (Negative Genetic)

ESM2 similar proteins: A0A0G2K344, A0A1B8YAB1, A2ALK8, A4IFG2, A9JRD8, B1H285, B3M1E1, B4GZ20, B4HJC0, B4KA23, B4QVW6, F7ASZ0, M3XQV7, P26045, P32871, P42336, P42337, P58544, P58545, Q08CL3, Q0V9W6, Q0VD31, Q16832, Q29B63, Q2LE78, Q3UQV5, Q5PQR3, Q5RAG3, Q5RGQ2, Q5TZE1, Q5ZIJ9, Q62371, Q62915, Q7K0L4, Q7Z7L7, Q8BH70, Q8BTI9, Q8C726, Q8K2J9, Q8LEV3

Diamond homologs: A2RUV9, A5A6K7, O14786, O17754, O18806, O35276, O35375, O35474, O43854, O54858, O54991, O60462, O75976, O88783, O89001, P00451, P02886, P02887, P02888, P04836, P12259, P12263, P14384, P15087, P15169, P16870, P21956, P28824, P29068, P37892, P39041, P42787, P70490, P78357, P79385, P79795, P83852, P97333, P97846, P98092

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
DDR2	up-regulates	SHC1	binding
SRC	up-regulates	DDR2	phosphorylation
regorafenib	“down-regulates activity”	DDR2	“chemical inhibition”
COL1A1	“up-regulates activity”	DDR2	binding
COL21A1	“up-regulates activity”	DDR2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by ERBB2	5	61.8×	7e-06
Diseases of signal transduction by growth factor receptors and second messengers	6	12.2×	1e-03
Signaling by Receptor Tyrosine Kinases	5	9.2×	4e-03
Cytokine Signaling in Immune system	5	7.3×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	36.4×	2e-04
positive regulation of ERK1 and ERK2 cascade	5	12.5×	4e-03
protein stabilization	6	11.8×	1e-03
negative regulation of apoptotic process	7	7.2×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — HCC.

Clinical variants and AI predictions

ClinVar

614 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	12
Uncertain significance	290
Likely benign	165
Benign	48

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1052169	NM_006182.4(DDR2):c.1382C>G (p.Ser461Ter)	Pathogenic
12314	NM_006182.4(DDR2):c.2177T>G (p.Ile726Arg)	Pathogenic
12315	NM_006182.4(DDR2):c.2138C>T (p.Thr713Ile)	Pathogenic
12316	NM_006182.4(DDR2):c.2283+1G>A	Pathogenic
1453437	NM_006182.4(DDR2):c.111del (p.Gly38fs)	Pathogenic
1459807	NM_006182.4(DDR2):c.2140C>T (p.Arg714Ter)	Pathogenic
1985374	NM_006182.4(DDR2):c.1021C>T (p.Arg341Ter)	Pathogenic
2002559	NC_000001.11:g.162775664_162775665insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGGAATGATTTTCTT	Pathogenic
2108672	NM_006182.4(DDR2):c.768T>A (p.Tyr256Ter)	Pathogenic
2145047	NM_006182.4(DDR2):c.1045C>T (p.Gln349Ter)	Pathogenic
223089	NM_001064.4(TKT):c.633G>A (p.Trp211Ter)	Pathogenic
223091	NM_001064.4(TKT):c.952C>T (p.Arg318Cys)	Pathogenic
2736527	NM_006182.4(DDR2):c.681del (p.Gly228_Leu229insTer)	Pathogenic
2772476	NM_006182.4(DDR2):c.2408_2409del (p.Glu803fs)	Pathogenic
2801612	NM_006182.4(DDR2):c.2125C>T (p.Arg709Ter)	Pathogenic
3247972	NC_000001.10:g.(?162740256)(162757423_?)del	Pathogenic
4720075	NM_006182.4(DDR2):c.1711G>T (p.Glu571Ter)	Pathogenic
60759	NM_006182.4(DDR2):c.337G>A (p.Glu113Lys)	Pathogenic
631572	NM_006182.4(DDR2):c.1831C>T (p.Arg611Ter)	Pathogenic
915984	GRCh37/hg19 1q23.3(chr1:162748370-162748520)	Pathogenic
12313	NM_006182.4(DDR2):c.2254C>T (p.Arg752Cys)	Likely pathogenic
1342148	NM_006182.4(DDR2):c.2323G>T (p.Val775Phe)	Likely pathogenic
2703347	NM_006182.4(DDR2):c.417+1G>T	Likely pathogenic
2705160	NM_006182.4(DDR2):c.565+1G>A	Likely pathogenic
3235058	NM_001064.4(TKT):c.181C>T (p.Gln61Ter)	Likely pathogenic
3641727	NM_006182.4(DDR2):c.186-1G>A	Likely pathogenic
3906889	NM_006182.4(DDR2):c.2416C>T (p.Arg806Ter)	Likely pathogenic
4073651	NM_006182.4(DDR2):c.2105C>T (p.Ser702Phe)	Likely pathogenic
4076974	NM_006182.4(DDR2):c.415C>T (p.Gln139Ter)	Likely pathogenic
4277802	NM_001064.4(TKT):c.1697-1G>A	Likely pathogenic

SpliceAI

3362 predictions. Top by Δscore:

Variant	Effect	Δscore
1:162632632:G:GG	donor_gain	1.0000
1:162719016:T:A	acceptor_gain	1.0000
1:162719019:A:AG	acceptor_gain	1.0000
1:162719020:T:G	acceptor_gain	1.0000
1:162719022:ATT:A	acceptor_gain	1.0000
1:162719024:T:A	acceptor_gain	1.0000
1:162752480:T:A	acceptor_gain	1.0000
1:162753077:T:A	acceptor_gain	1.0000
1:162753078:G:A	acceptor_gain	1.0000
1:162753087:T:A	acceptor_gain	1.0000
1:162753093:A:AG	acceptor_gain	1.0000
1:162753094:G:GG	acceptor_gain	1.0000
1:162753094:G:GT	acceptor_loss	1.0000
1:162753094:GC:G	acceptor_gain	1.0000
1:162753094:GCT:G	acceptor_gain	1.0000
1:162753094:GCTA:G	acceptor_gain	1.0000
1:162753094:GCTAT:G	acceptor_gain	1.0000
1:162754851:AACAG:A	donor_loss	1.0000
1:162754852:ACAGG:A	donor_loss	1.0000
1:162754853:CAGGT:C	donor_loss	1.0000
1:162754854:AGGTA:A	donor_loss	1.0000
1:162754855:GGTA:G	donor_loss	1.0000
1:162754857:T:A	donor_loss	1.0000
1:162755152:TCA:T	acceptor_loss	1.0000
1:162755153:CAG:C	acceptor_loss	1.0000
1:162755154:A:AG	acceptor_gain	1.0000
1:162755155:G:A	acceptor_loss	1.0000
1:162755155:G:GG	acceptor_gain	1.0000
1:162755155:GGT:G	acceptor_gain	1.0000
1:162755300:CTAG:C	donor_loss	1.0000

AlphaMissense

5681 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:162754652:T:A	W72R	1.000
1:162754652:T:C	W72R	1.000
1:162772233:G:A	G572R	1.000
1:162772233:G:C	G572R	1.000
1:162772239:T:C	F574L	1.000
1:162772241:T:A	F574L	1.000
1:162772241:T:G	F574L	1.000
1:162776207:T:A	V707D	1.000
1:162776213:G:C	R709P	1.000
1:162776216:A:C	D710A	1.000
1:162776216:A:G	D710G	1.000
1:162776216:A:T	D710V	1.000
1:162776217:T:A	D710E	1.000
1:162776217:T:G	D710E	1.000
1:162776219:T:C	L711P	1.000
1:162776232:C:A	N715K	1.000
1:162776232:C:G	N715K	1.000
1:162776235:T:G	C716W	1.000
1:162776270:A:T	D728V	1.000
1:162776333:T:A	L749H	1.000
1:162776333:T:C	L749P	1.000
1:162776341:C:A	R752S	1.000
1:162776344:T:A	W753R	1.000
1:162776344:T:C	W753R	1.000
1:162776346:G:C	W753C	1.000
1:162776346:G:T	W753C	1.000
1:162776348:T:C	M754T	1.000
1:162776353:T:A	W756R	1.000
1:162776353:T:C	W756R	1.000
1:162776359:A:C	S758R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000438 (1:162703318 A>G), RS1000008374 (1:162747440 A>C,G), RS1000049257 (1:162718061 C>T), RS1000050 (1:162766673 C>T), RS1000057182 (1:162760836 C>T), RS1000066486 (1:162642970 G>A), RS1000067005 (1:162652953 A>C,G), RS1000067569 (1:162754323 A>G,T), RS1000098340 (1:162754014 G>A), RS1000103792 (1:162668062 G>T), RS1000107139 (1:162751656 C>T), RS1000148849 (1:162728086 A>C), RS1000149820 (1:162668170 G>T), RS1000153057 (1:162710061 G>A), RS1000171825 (1:162711799 T>A,C)

Disease associations

OMIM: gene MIM:191311 | disease phenotypes: MIM:271665, MIM:617044, MIM:618175

GenCC curated gene-disease

Disease	Classification	Inheritance
spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	Definitive	Autosomal recessive
warburg-cinotti syndrome	Strong	Autosomal dominant
transketolase deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	Definitive	AR
warburg-cinotti syndrome	Moderate	AD

Mondo (7): spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (MONDO:0010077), transketolase deficiency (MONDO:0014881), warburg-cinotti syndrome (MONDO:0032579), connective tissue disorder (MONDO:0003900), lung adenocarcinoma (MONDO:0005061), squamous cell lung carcinoma (MONDO:0005097), fetal growth restriction (MONDO:0005030)

Orphanet (3): Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (Orphanet:93358), Transketolase deficiency (Orphanet:488618), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

127 total (30 of 127 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000107	Renal cyst
HP:0000212	Gingival overgrowth
HP:0000218	High palate
HP:0000260	Wide anterior fontanel
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000283	Broad face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000331	Short chin
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000405	Conductive hearing impairment
HP:0000413	Atresia of the external auditory canal
HP:0000430	Underdeveloped nasal alae
HP:0000457	Depressed nasal ridge
HP:0000460	Narrow nose
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000509	Conjunctivitis
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000520	Proptosis
HP:0000554	Uveitis

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST003598_29	QRS duration	6.000000e-09
GCST003598_50	QRS duration	3.000000e-06
GCST003844_27	QRS duration	7.000000e-10
GCST004250_15	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	2.000000e-06
GCST004858_3	Dupuytren’s disease	2.000000e-10
GCST005951_50	Body mass index	5.000000e-11
GCST007103_8	QRS duration	2.000000e-08
GCST007104_8	QRS duration	4.000000e-23
GCST008839_498	Height	6.000000e-09
GCST010002_424	Refractive error	9.000000e-24
GCST010796_3855	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-14
GCST010796_3856	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-18
GCST010796_3857	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-22
GCST011438_1	Glaucoma (primary open-angle)	6.000000e-07
GCST011439_17	Glaucoma (primary open-angle)	7.000000e-09
GCST012020_94	Serum metabolite levels	5.000000e-13
GCST012020_95	Serum metabolite levels	1.000000e-16
GCST90020024_1220	A body shape index	1.000000e-08
GCST90020024_1221	A body shape index	9.000000e-12
GCST90020025_1356	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST90020025_1357	Waist-to-hip ratio adjusted for BMI	3.000000e-10
GCST90020027_254	Waist-hip index	5.000000e-09
GCST90020027_255	Waist-hip index	4.000000e-10
GCST90020029_1206	Waist circumference adjusted for body mass index	7.000000e-09
GCST90020029_1207	Waist circumference adjusted for body mass index	2.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005054	QRS complex
EFO:0007965	response to combination chemotherapy
EFO:0004229	Dupuytren Contracture
EFO:0004340	body mass index
EFO:0004327	electrocardiography
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
D005317	Fetal Growth Retardation	C12.050.703.277.370; C16.300.390; C23.550.393.450
C564794	Spondylometaepiphyseal Dysplasia, Short Limb-Hand Type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5122 (SINGLE PROTEIN), CHEMBL6195682 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

59 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 695,392 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1554	DACTINOMYCIN	4	175,245
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL941	IMATINIB	4	111,611
CHEMBL1908391	MASITINIB	3
CHEMBL217092	SARACATINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL3544983	TESEVATINIB	3
CHEMBL4583691	NAPORAFENIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2

Clinical evidence (CIViC)

Drug × variant × indication: 7 predictive associations from 7 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
DDR2 S768R	Erlotinib + Dasatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID272
DDR2 G253C	Dasatinib	Cancer	Sensitivity/Response	CIViC D	EID266
DDR2 G505S	Dasatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC D	EID267
DDR2 G774V	Dasatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC D	EID268
DDR2 I638F	Dasatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC D	EID269
DDR2 L239R	Dasatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC D	EID270
DDR2 L63V	Dasatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC D	EID271

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type XVI RTKs: DDR (collagen receptor) family

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
nilotinib	Inhibition	9.3	pIC50
sitravatinib	Inhibition	9.3	pIC50
naporafenib	Inhibition	8.0	pKd
sorafenib	Inhibition	8.0	pIC50
RIPK3 inhibitor 18	Inhibition	7.96	pIC50
DDR1/2 inhibitor 5n	Inhibition	7.69	pIC50
DDR1 inhibitor 7rh	Inhibition	6.99	pIC50
compound 1 [PMID: 31477924]	Inhibition	6.63	pIC50
DDR-IN-1	Inhibition	6.38	pIC50
imatinib	Inhibition	6.17	pIC50

Binding affinities (BindingDB)

70 measured of 96 human assays (96 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
Staurosporine	KD	1.7 nM
4-amino-N-[1-(4-chloroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide	IC50	5 nM	US-9156852: Thieno[3,2-D]pyrimidine derivatives having inhibitory activity for protein kinases
Butyl 4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)-piperazine-1-carboxylate (3e)	IC50	6.16 nM
2-((6-(4-Acryloylpiperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)-thiazole-5-carboxamide (3l)	IC50	6.29 nM
Methyl 4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)-piperazine-1-carboxylate (3a)	IC50	6.76 nM
2-Morpholinoethyl 4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)-piperazine-1-carboxylate (3j)	IC50	7.04 nM
2-(Dimethylamino)ethyl 4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)-piperazine-1-carboxylate (3k)	IC50	7.89 nM
(E)-2-((6-(4-(but-2-enoyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide (3m)	IC50	8.34 nM
2-Chloroethyl 4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)-piperazine-1-carboxylate (3i)	IC50	9 nM
4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole	KD	9.8 nM
N-[1-(4-acetylanilino)-6-methylisoquinolin-5-yl]-4-aminothieno[3,2-d]pyrimidine-7-carboxamide	IC50	10 nM	US-9156852: Thieno[3,2-D]pyrimidine derivatives having inhibitory activity for protein kinases
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	IC50	10 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
Ethyl 4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)-piperazine-1-carboxylate (3b)	IC50	11.4 nM
4-[4-(4-fluorophenyl)-2-(4-methanesulfinylphenyl)-1H-imidazol-5-yl]pyridine	KD	12 nM
Isopropyl 4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)-piperazine-1-carboxylate (3c)	IC50	14 nM
Allyl 3-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)pyrrolidine-1-carboxylate (5d)	IC50	17 nM
N-[3-[2-[4-amino-1-(1-methylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-3-(trifluoromethyl)benzamide	IC50	18 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
5-[(2-methyl-5-{[3-(trifluoromethyl)phenyl]carbamoyl}phenyl)amino]pyridine-3-carboxamide	IC50	19 nM
Phenyl 4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)-piperazine-1-carboxylate (3g)	IC50	21.3 nM
Allyl 4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)-piperazine-1-carboxylate (3d)	IC50	21.6 nM
5-((2-Methyl-5-((3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl)carbamoyl)phenyl)amino)nicotinamide (3)	IC50	22 nM
Ethyl 3-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)pyrrolidine-1-carboxylate (5b)	IC50	22.4 nM
N-(2-chloro-6-methylphenyl)-2-((2-methyl-6-((1-propionylpyrrolidin-3-yl)amino)pyrimidin-4-yl)amino)thiazole-5-carboxamide (5l)	IC50	23.9 nM
BMS-354825	KD	27 nM
Methyl 3-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)pyrrolidine-1-carboxylate (5a)	IC50	32.9 nM
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide	IC50	33 nM
2-((6-((1-Acryloylpyrrolidin-3-yl)amino)-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide (5k)	IC50	34.4 nM
Isobutyl 4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)-piperazine-1-carboxylate (3f)	IC50	34.6 nM
N-(2-chloro-6-methylphenyl)-2-((2-methyl-6-((1-(methylsulfonyl)pyrrolidin-3-yl)amino)-pyrimidin-4-yl)amino)thiazole-5-carboxamide (5i)	IC50	38.3 nM
4-amino-N-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide	IC50	44 nM	US-9156852: Thieno[3,2-D]pyrimidine derivatives having inhibitory activity for protein kinases
N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-2-(4-(isoquinolin-7-yl)phenyl)acetamide (4)	IC50	46 nM
N-[5-({4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}carbamoyl)-2-methylphenyl]-5-(thiophen-2-yl)pyridine-3-carboxamide (6)	IC50	51 nM
N-(5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)-2-methylphenyl)-5-(1-methyl-1H-pyrazol-4-yl)nicotinamide (5)	IC50	56 nM
Phenyl 3-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)pyrrolidine-1-carboxylate (5g)	IC50	59.9 nM
Isopropyl 3-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)pyrrolidine-1-carboxylate (5c)	IC50	72.1 nM
Isobutyl 3-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)pyrrolidine-1-carboxylate (5f)	IC50	85.4 nM
4-amino-N-[1-(3-chloroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide	IC50	93 nM	US-9156852: Thieno[3,2-D]pyrimidine derivatives having inhibitory activity for protein kinases
Butyl 3-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)pyrrolidine-1-carboxylate (5e)	IC50	123 nM
Benzyl 4-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)-piperazine-1-carboxylate (3h)	IC50	133 nM
DDR1-IN-2	IC50	145 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
N-(2-chloro-6-methylphenyl)-2-((6-((1-(ethylsulfonyl)pyrrolidin-3-yl)amino)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide (5j)	IC50	156 nM
4-amino-N-[1-(3-chloro-4-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide	IC50	181 nM	US-9156852: Thieno[3,2-D]pyrimidine derivatives having inhibitory activity for protein kinases
Benzyl 3-(6-((5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)amino)-2-methylpyrimidin-4-yl)pyrrolidine-1-carboxylate (5h)	IC50	285 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
N-{4-methyl-3-[(2-oxo-1,3-dihydroindol-5-yl)oxy]phenyl}-4-[(1-methylpiperidin-4-yl)oxy]-3- (trifluoromethyl)benzamide (2)	IC50	388 nM
DDR1-IN-1	IC50	413 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
D2190	IC50	546 nM	US-10370360: Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof

ChEMBL bioactivities

525 potent at pChembl≥5 of 541 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL5938192
10.00	IC50	0.1	nM	CHEMBL5787536
10.00	IC50	0.1	nM	CHEMBL5781115
10.00	IC50	0.1	nM	CHEMBL5965095
9.70	IC50	0.2	nM	CHEMBL5885968
9.70	IC50	0.2	nM	CHEMBL6051298
9.70	IC50	0.2	nM	CHEMBL5756960
9.52	IC50	0.3	nM	CHEMBL6055194
9.52	IC50	0.3	nM	CHEMBL6052146
9.52	IC50	0.3	nM	CHEMBL6027087
9.44	IC50	0.367	nM	STAUROSPORINE
9.40	IC50	0.4	nM	DASATINIB
9.40	IC50	0.4	nM	CHEMBL5758698
9.40	IC50	0.4	nM	CHEMBL6044993
9.30	IC50	0.5	nM	CHEMBL5829475
9.30	IC50	0.5	nM	CHEMBL5518031
9.27	EC50	0.54	nM	BAY-826
9.22	Kd	0.6	nM	CHEMBL2336015
9.22	IC50	0.6	nM	CHEMBL5848200
9.19	IC50	0.65	nM	STAUROSPORINE
9.15	IC50	0.7	nM	CHEMBL5986782
9.12	IC50	0.75	nM	SR-302
9.10	IC50	0.8	nM	CHEMBL4062877
9.10	IC50	0.8	nM	CHEMBL5974437
9.00	IC50	1	nM	CHEMBL2403816
9.00	IC50	1	nM	CHEMBL5906159
8.96	IC50	1.1	nM	CHEMBL5900841
8.92	IC50	1.19	nM	STAUROSPORINE
8.92	IC50	1.2	nM	CHEMBL4443643
8.89	Kd	1.3	nM	BAY-826
8.85	IC50	1.4	nM	DASATINIB
8.82	IC50	1.5	nM	CHEMBL4448547
8.74	IC50	1.8	nM	STAUROSPORINE
8.70	IC50	2	nM	CHEMBL2403875
8.70	IC50	2	nM	NILOTINIB
8.70	IC50	2	nM	CHEMBL1738943
8.70	IC50	2	nM	DASATINIB
8.68	IC50	2.1	nM	CHEMBL5931136
8.66	IC50	2.2	nM	CHEMBL5542762
8.64	IC50	2.3	nM	CHEMBL5752611
8.59	IC50	2.6	nM	CHEMBL4466555
8.59	IC50	2.6	nM	CHEMBL4559322
8.59	IC50	2.6	nM	CHEMBL4535267
8.59	IC50	2.6	nM	CHEMBL1688860
8.57	IC50	2.7	nM	CHEMBL4460782
8.57	IC50	2.7	nM	CHEMBL4525313
8.55	IC50	2.8	nM	CHEMBL5752161
8.54	IC50	2.9	nM	CHEMBL4572126
8.52	IC50	3	nM	CHEMBL2403816
8.52	Kd	3	nM	DASATINIB

PubChem BioAssay actives

458 with measured affinity, of 1488 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	1141136: Inhibition of wild type DDR2 (unknown origin) preincubated for 30 mins before substrate addition by FRET assay	ic50	0.0004	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715380: Inhibition of human DDR2 using KKSRGDYMTMQIG as substrate by [gamma-33P]-ATP assay	ic50	0.0004	uM
Nilotinib	1800098: EC50 Test from Article 10.1021/cb400430t: “Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor.”	ic50	0.0005	uM
4-ethyl-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamide	1202720: Binding affinity to DDR2 (unknown origin) by active-site dependent competition binding assay	kd	0.0006	uM
4-fluoro-2-[5-[[(1R)-2-hydroxy-1-phenylethyl]amino]-3-(3-methyl-2H-indazol-5-yl)-2-pyridinyl]phenol	1450711: Inhibition of recombinant DDR2 (unknown origin) using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0008	uM
1-[1-(3-aminophenyl)-3-tert-butylpyrazol-5-yl]-3-[4-(quinazolin-4-ylamino)phenyl]urea	1141137: Inhibition of DDR2 T654M mutant (unknown origin) preincubated for 30 mins before substrate addition by FRET assay	ic50	0.0010	uM
3-(1H-indazol-6-yl)-4-methyl-N-(3-propan-2-ylphenyl)benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0012	uM
3-cyano-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	2155085: Binding affinity to DDR2 (unknown origin) assessed as dissociation constant by KINOME scan assay	kd	0.0013	uM
3-(1H-indazol-6-yl)-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0015	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-[2-(pyridin-4-ylmethoxy)ethyl]-1,3-thiazol-2-yl]urea	1141137: Inhibition of DDR2 T654M mutant (unknown origin) preincubated for 30 mins before substrate addition by FRET assay	ic50	0.0020	uM
1-[1-(3-aminophenyl)-3-tert-butylpyrazol-5-yl]-3-[3-(quinazolin-4-ylamino)phenyl]urea	1141136: Inhibition of wild type DDR2 (unknown origin) preincubated for 30 mins before substrate addition by FRET assay	ic50	0.0020	uM
4-methyl-3-[2-[(1-methylpyrazol-4-yl)amino]quinazolin-6-yl]-N-[3-(trifluoromethyl)phenyl]benzamide	2074655: Inhibition of flag-tagged DDR2 (unknown origin) by TR-FRET assay	ic50	0.0022	uM
N-[4-chloro-3-(trifluoromethyl)phenyl]-4-methyl-3-[[1-(7H-purin-6-yl)cyclopropanecarbonyl]amino]benzamide	1534562: Inhibition of human DDR2 using KKSRGDYMTMQIG as substrate by [gamma-33P]-ATP assay	ic50	0.0026	uM
3-[3-(1-ethylpyrazol-4-yl)-1H-indazol-6-yl]-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0026	uM
4-methyl-3-[3-[1-(2-morpholin-4-ylethyl)pyrazol-4-yl]-1H-indazol-6-yl]-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0026	uM
3-[(dimethylamino)methyl]-N-[(2R)-7-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1,2,3,4-tetrahydronaphthalen-2-yl]-5-(trifluoromethyl)benzamide	586442: Inhibition of DDR2	ic50	0.0026	uM
3-[3-[1-[2-(dimethylamino)-2-oxoethyl]pyrazol-4-yl]-1H-indazol-6-yl]-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0027	uM
N-[3-(2-cyanopropan-2-yl)phenyl]-3-(1H-indazol-6-yl)-4-methylbenzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0027	uM
3-[3-[1-(2-hydroxyethyl)pyrazol-4-yl]-1H-indazol-6-yl]-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0029	uM
3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-4-methyl-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]benzamide	1356712: Inhibition of DDR2 (unknown origin) incubated for 1 hr using fluorescein-poly-GAT substrate by TR-FRET based LANCE ULTRA kinase assay	ic50	0.0031	uM
3-[3-(1-cyclopropylpyrazol-4-yl)-1H-indazol-6-yl]-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0032	uM
4-methyl-3-[3-(1-propylpyrazol-4-yl)-1H-indazol-6-yl]-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0032	uM
N-[5-[[(3-fluorophenyl)carbamoylamino]methyl]-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide	1242616: Inhibition of DDR2 (unknown origin) after 1 hr by time resolved fluorescence method	ic50	0.0033	uM
N-[3-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]-5-(trifluoromethyl)phenyl]-3-(1H-indazol-6-yl)-4-methylbenzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0034	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	624777: Binding constant for DDR2 kinase domain	kd	0.0036	uM
3-[3-[1-(2-hydroxypropyl)pyrazol-4-yl]-1H-indazol-6-yl]-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0037	uM
4-methyl-3-[3-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]-1H-indazol-6-yl]-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0038	uM
1-[1-(3-aminophenyl)-3-tert-butylpyrazol-5-yl]-3-(4-chlorophenyl)urea	1141132: Binding affinity to human acrylodan-labeled N-terminal His-tagged DDR2 (558 to 855 aa) by fluorescence spectroscopy	kd	0.0038	uM
N-[3-[(4-ethylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-3-(1H-indazol-6-yl)-4-methylbenzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0039	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1424973: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0040	uM
4-methyl-3-[3-(1-methylpyrazol-4-yl)-1H-indazol-6-yl]-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0044	uM
N-[5-[(1S)-1-[(3-fluorophenyl)carbamoylamino]ethyl]-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide	1242616: Inhibition of DDR2 (unknown origin) after 1 hr by time resolved fluorescence method	ic50	0.0045	uM
4-methyl-3-[[5-(1-methylpyrazol-3-yl)-3-pyridinyl]methylamino]-N-[3-(trifluoromethyl)phenyl]benzamide	1541771: Inhibition of kinase tracer 178 binding to recombinant human His-tagged DDR2 expressed in baculovirus infected Sf9 cells incubated for 1 hr by TR-FRET based LanthaScreen Eu kinase binding assay	ic50	0.0046	uM
3-(1H-indazol-6-yl)-4-methyl-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0047	uM
5-[[2-methyl-5-[[3-(trifluoromethyl)phenyl]carbamoyl]anilino]methyl]pyridine-3-carboxamide	1541771: Inhibition of kinase tracer 178 binding to recombinant human His-tagged DDR2 expressed in baculovirus infected Sf9 cells incubated for 1 hr by TR-FRET based LanthaScreen Eu kinase binding assay	ic50	0.0048	uM
3-[(3-carbamoylphenyl)methylamino]-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide	2074665: Inhibition of DDR2 (unknown origin) by ADP-Glo assay	ic50	0.0048	uM
N-[1-[4-[[(2R)-4-cyclohexyl-1-[(1-methylsulfonylpiperidin-3-yl)amino]-1-oxobutan-2-yl]carbamoyl]phenyl]ethyl]imidazo[1,2-a]pyridine-3-carboxamide	1830183: Inhibition of DDR2 (unknown origin) expressed in HEK293T cells using NanoBRET NanoGlo substrate incubated for 2 hrs by NanoBRET assay	ic50	0.0050	uM
N-[(1S)-3,3-difluoro-1-(4-methylpiperazin-1-yl)-1,2-dihydroinden-5-yl]-4-fluoro-3-[2-(5-morpholin-4-yl-3-pyridinyl)ethynyl]benzamide	2099926: Inhibition of DDR2 (unknown origin) using FAM-P22 peptide as substrate preincubated with compound for 10 mins followed by substrate addition and ATP measured after 60 mins by fluorescence-based microfluidic mobility shift assay	ic50	0.0051	uM
4-methyl-3-[3-[1-(oxan-2-yl)pyrazol-4-yl]-1H-indazol-6-yl]-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0052	uM
N-[3-(1H-indazol-6-yl)-4-methylphenyl]-3-(trifluoromethyl)benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0055	uM
4-methyl-N-[3-methyl-5-(4-methylimidazol-1-yl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide	722265: Binding affinity to human DDR2	kd	0.0056	uM
N-[2-methyl-5-[(1S)-1-[[3-(trifluoromethyl)benzoyl]amino]ethyl]phenyl]imidazo[1,2-a]pyridine-3-carboxamide	1242616: Inhibition of DDR2 (unknown origin) after 1 hr by time resolved fluorescence method	ic50	0.0058	uM
3-[[2-[3-(morpholin-4-ylmethyl)phenyl]thieno[3,2-b]pyridin-7-yl]amino]phenol	1202716: Inhibition of recombinant activated DDR2 tyrosine kinase domain (unknown origin) using histone H2B peptide substrate and [32P]ATP incubated for 15 mins	ic50	0.0060	uM
N-[4-[4-[[[4-chloro-2-[2-(dimethylamino)ethoxy]-5-methylphenyl]carbamoylamino]methyl]-2-methylphenoxy]-2-pyridinyl]acetamide	1202725: Inhibition of human DDR2 expressed in HEK293 cells assessed as reduction in collagen-2-induced DDR2 phosphorylation	ic50	0.0060	uM
4-cyclopropyl-3-[2-[(1-cyclopropylpyrazol-4-yl)amino]quinazolin-6-yl]-N-[3-(trifluoromethyl)phenyl]benzamide	2074655: Inhibition of flag-tagged DDR2 (unknown origin) by TR-FRET assay	ic50	0.0061	uM
N-[5-[(1S)-1-[(5-fluoro-1,3-benzoxazol-2-yl)amino]ethyl]-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide	1242616: Inhibition of DDR2 (unknown origin) after 1 hr by time resolved fluorescence method	ic50	0.0061	uM
butyl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazine-1-carboxylate	1802639: LanthaScreen Eu Kinase Activity Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0062	uM
4-methyl-3-[3-[1-(oxolan-3-yl)pyrazol-4-yl]-1H-indazol-6-yl]-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0062	uM
4-methyl-3-[3-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-indazol-6-yl]-N-[3-(trifluoromethyl)phenyl]benzamide	1612903: Inhibition of DDR2 (unknown origin) using poly (Glu, Tyr) 4:1 substrate after 60 mins by ELISA	ic50	0.0062	uM
N-(2-chloro-6-methylphenyl)-2-[[2-methyl-6-(4-prop-2-enoylpiperazin-1-yl)pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1802639: LanthaScreen Eu Kinase Activity Assay from Article 10.1111/cbdd.12863: “Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.”	ic50	0.0063	uM

CTD chemical–gene interactions

64 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
titanium dioxide	increases expression, affects binding	2
sodium arsenite	increases expression	2
mercuric bromide	affects cotreatment, increases expression	2
perfluorooctane sulfonic acid	increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Hydrogen Peroxide	affects expression, decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tretinoin	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
FR900359	decreases phosphorylation	1
geldanamycin	increases expression	1
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
bisphenol A	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
ferrous chloride	increases expression	1
nickel sulfate	increases expression	1
beta-methylcholine	affects expression	1
naphthenic acid	increases expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
3-nitrobenzanthrone	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
perfluorohexanesulfonic acid	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1

ChEMBL screening assays

389 unique, capped per target: 386 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1034100	Binding	Inhibition of DDR2 at 3 uM	Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem
CHEMBL4407670	ADMET	Inhibition of GST-tagged recombinant human DDR2 expressed in baculovirus using fluorescein-poly GAT as substrate after 1 hr by FRET-based LanthaScreen Eu kinase binding assay	2-Amino-2,3-dihydro-1H-indene-5-carboxamide-Based Discoidin Domain Receptor 1 (DDR1) Inhibitors: Design, Synthesis, and in Vivo Antipancreatic Cancer Efficacy. — J Med Chem

Cellosaurus cell lines

12 cell lines: 11 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1590	NCI-H810	Cancer cell line	Male
CVCL_2891	EBC-1	Cancer cell line	Male
CVCL_B1PY	Abcam HeLa DDR2 KO	Cancer cell line	Female
CVCL_B8EL	Abcam HCT 116 DDR2 KO	Cancer cell line	Male
CVCL_B8UQ	Abcam MCF-7 DDR2 KO	Cancer cell line	Female
CVCL_B9GU	Abcam A-549 DDR2 KO	Cancer cell line	Male
CVCL_JY47	PLT460F_(DDR2)	Transformed cell line	Female
CVCL_LC83	EBC-1 KRAS (G12D/+/+/+)	Cancer cell line	Male
CVCL_SK61	HAP1 DDR2 (-) 1	Cancer cell line	Male
CVCL_SK62	HAP1 DDR2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

297 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)
NCT06031246	PHASE3	RECRUITING	Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018)
NCT06634966	PHASE3	RECRUITING	Segmentectomy for Solid-dominant Lung Cancer
NCT07169903	PHASE3	NOT_YET_RECRUITING	Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT
NCT07481786	PHASE3	RECRUITING	Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD