DDR1

Summary

DDR1 (discoidin domain receptor tyrosine kinase 1, HGNC:2730) is a protein-coding gene on chromosome 6p21.33, encoding Epithelial discoidin domain-containing receptor 1 (Q08345). Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation.

Receptor tyrosine kinases play a key role in the communication of cells with their microenvironment. These kinases are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. Expression of this protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, it has been shown to be significantly overexpressed in several human tumors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 780 — RefSeq curated summary.

At a glance

• Gene–disease (curated): chondrodysplasia (Limited, GenCC)
• GWAS associations: 38
• Clinical variants (ClinVar): 147 total
• Druggable target: yes — 77 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001297654

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2730
Approved symbol	DDR1
Name	discoidin domain receptor tyrosine kinase 1
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	RTK6, CD167
Ensembl gene	ENSG00000204580
Ensembl biotype	protein_coding
OMIM	600408
Entrez	780

Gene structure

Transcript identifiers

Ensembl transcripts: 126 — 111 protein_coding, 6 retained_intron, 6 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000324771, ENST00000376567, ENST00000376568, ENST00000376569, ENST00000376570, ENST00000376575, ENST00000396342, ENST00000412274, ENST00000417521, ENST00000418800, ENST00000421124, ENST00000424544, ENST00000428153, ENST00000431373, ENST00000437124, ENST00000446312, ENST00000452441, ENST00000454612, ENST00000460944, ENST00000465966, ENST00000482050, ENST00000482873, ENST00000484556, ENST00000485023, ENST00000502955, ENST00000503180, ENST00000503495, ENST00000503628, ENST00000503670, ENST00000504152, ENST00000504651, ENST00000504679, ENST00000504927, ENST00000505066, ENST00000505534, ENST00000506573, ENST00000507046, ENST00000507533, ENST00000507901, ENST00000508312, ENST00000508317, ENST00000508472, ENST00000509639, ENST00000511510, ENST00000512336, ENST00000512694, ENST00000512725, ENST00000513043, ENST00000513240, ENST00000513243, ENST00000513514, ENST00000513749, ENST00000514434, ENST00000514534, ENST00000515219, ENST00000515233, ENST00000515529, ENST00000515881, ENST00000908924, ENST00000908925, ENST00000908926, ENST00000908927, ENST00000908928, ENST00000908929, ENST00000908930, ENST00000908931, ENST00000908932, ENST00000908933, ENST00000908934, ENST00000908935, ENST00000908936, ENST00000908937, ENST00000908938, ENST00000908939, ENST00000908940, ENST00000908941, ENST00000908942, ENST00000908943, ENST00000908944, ENST00000908945, ENST00000908946, ENST00000908947, ENST00000908948, ENST00000908949, ENST00000908950, ENST00000908951, ENST00000908952, ENST00000908953, ENST00000908954, ENST00000908955, ENST00000908956, ENST00000908957, ENST00000908958, ENST00000937421, ENST00000937422, ENST00000937423, ENST00000937424, ENST00000937425, ENST00000937426, ENST00000937427, ENST00000937428, ENST00000937429, ENST00000937430, ENST00000937431, ENST00000937432, ENST00000937433, ENST00000937434, ENST00000937435, ENST00000937436, ENST00000937437, ENST00000937438, ENST00000937439, ENST00000937440, ENST00000937441, ENST00000937442, ENST00000956419, ENST00000956420, ENST00000956421, ENST00000956422, ENST00000956423, ENST00000956424, ENST00000956425, ENST00000956426, ENST00000956427, ENST00000956428, ENST00000956429

RefSeq mRNA: 37 — MANE Select: NM_001297654 NM_001202521, NM_001202522, NM_001202523, NM_001297652, NM_001297653, NM_001297654, NM_001387892, NM_001387893, NM_001387894, NM_001387895, NM_001387896, NM_001387897, NM_001387898, NM_001387899, NM_001387900, NM_001387901, NM_001387902, NM_001387903, NM_001387904, NM_001387905, NM_001387906, NM_001387907, NM_001387908, NM_001387909, NM_001387910, NM_001387911, NM_001387912, NM_001387913, NM_001387914, NM_001387915, NM_001387916, NM_001387917, NM_001387918, NM_001410869, NM_001954, NM_013993, NM_013994

CCDS: CCDS34385, CCDS4690, CCDS47396, CCDS75419, CCDS93879

Canonical transcript exons

ENST00000376568 — 18 exons

Exon	Start	End
ENSE00001599026	30899156	30900156
ENSE00001648581	30884519	30884710
ENSE00003458974	30897379	30897597
ENSE00003466301	30897014	30897141
ENSE00003480800	30895404	30895514
ENSE00003484441	30888908	30889010
ENSE00003497868	30892002	30892188
ENSE00003519759	30894506	30894671
ENSE00003520835	30896621	30896865
ENSE00003564755	30898888	30899037
ENSE00003578260	30889202	30889430
ENSE00003621333	30890973	30891120
ENSE00003632050	30898073	30898307
ENSE00003644066	30893272	30893423
ENSE00003646071	30893068	30893163
ENSE00003653022	30892296	30892542
ENSE00003653816	30888688	30888814
ENSE00003685335	30891380	30891479

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.0910 / max 542.7415, expressed in 1679 samples.

FANTOM5 promoters (25 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66823	16.0521	1635
66816	10.2478	699
66812	2.3330	276
66811	1.8801	259
66822	1.4218	723
66825	1.3594	498
66829	0.7557	338
66820	0.7272	254
66813	0.5840	189
66833	0.3879	101

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.18	gold quality
right uterine tube	UBERON:0001302	99.13	gold quality
ganglionic eminence	UBERON:0004023	98.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.45	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.35	gold quality
minor salivary gland	UBERON:0001830	98.09	gold quality
saliva-secreting gland	UBERON:0001044	98.08	gold quality
islet of Langerhans	UBERON:0000006	98.00	gold quality
skin of abdomen	UBERON:0001416	97.96	gold quality
esophagus mucosa	UBERON:0002469	97.92	gold quality
metanephros cortex	UBERON:0010533	97.86	gold quality
zone of skin	UBERON:0000014	97.82	gold quality
substantia nigra	UBERON:0002038	97.73	gold quality
skin of leg	UBERON:0001511	97.69	gold quality
pancreas	UBERON:0001264	97.55	gold quality
cortex of kidney	UBERON:0001225	97.40	gold quality
left lobe of thyroid gland	UBERON:0001120	97.38	gold quality
thyroid gland	UBERON:0002046	97.27	gold quality
body of pancreas	UBERON:0001150	97.25	gold quality
temporal lobe	UBERON:0001871	97.11	gold quality
amygdala	UBERON:0001876	97.09	gold quality
right lobe of thyroid gland	UBERON:0001119	96.94	gold quality
hypothalamus	UBERON:0001898	96.94	gold quality
gall bladder	UBERON:0002110	96.78	gold quality
cortical plate	UBERON:0005343	96.63	gold quality
duodenum	UBERON:0002114	96.57	gold quality
Ammon’s horn	UBERON:0001954	96.54	gold quality
lower esophagus mucosa	UBERON:0035834	96.38	gold quality
pituitary gland	UBERON:0000007	96.30	gold quality
mucosa of transverse colon	UBERON:0004991	96.27	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.70
E-GEOD-75367	no	47.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HES1, HEY2, TP53, TP63

miRNA regulators (miRDB)

39 targeting DDR1, 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-6876-5P	100.00	67.68	2126
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-198	98.70	67.32	920
HSA-MIR-6852-3P	98.54	67.60	1468

Literature-anchored findings (GeneRIF, showing 40)

• gene expression analysis with DDR1 overexpression, using microarrays specific for human and mouse genes coding for extracellular matrix proteins or ECM-interacting factors (PMID:12935821)
• The interaction of DDR1b isoform with collagen up-regulates the production of IL-8, macrophage inflammatory protein-1 alpha, and monocyte chemoattractant protein-1 in macrophages in a p38 mitogen-activated protein kinase- and NF-kappa B-dependent manner. (PMID:14764702)
• 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)
• several residues within loop 1 (Ser-52-Thr-57) and loop 3 (Arg-105-Lys-112) as well as Ser-175 in loop 4 of DDR1 are critically involved in collagen binding (PMID:15136580)
• up-regulation of DDR1, CLDN3, and epithelial cell adhesion molecule are early events in the development of epithelial ovarian cancer (PMID:15240533)
• The results demonstrate that collagen-evoked ectodomain cleavage of DDR1 is mediated in part by Src-dependent activation (PMID:16440311)
• dimeric receptor tyrosine kinase DDR1 requires a transmembrane leucine zipper for activation (PMID:16774916)
• DDR1 signaling provides a novel target for therapeutic intervention with the prosurvival/antiapoptotic machinery of tumor cells. (PMID:16912190)
• Results strongly suggest that DDR1 mediates cell invasion-related signaling between collagen type I and MMP-2 and -9 in pituitary adenoma cells. (PMID:17001518)
• Thus, DARPP-32 signaling downstream of DDR1 is a potential new target for effective anti-metastatic breast cancer therapy (PMID:17027969)
• DDR1 knockdown decreased melanocyte adhesion to collagen IV and shifted melanocyte localization in a manner similar to CCN3 knockdown. (PMID:17101694)
• altered expression of DDR1 may contribute to malignant progression of non-small cell lung carcinoma (PMID:17299390)
• In the present study we screened for single nucleotide polymorphisms (SNPs) in the DNA from 100 schizophrenia patients. We identified mutation within exon 10 that produces the amino-acid substitution N502S in the a-d isoforms, and M475V in the e isoform. (PMID:17440435)
• DDR1 gene may be regarded as a potential marker for some types of endometrial cancer. (PMID:17704737)
• PCA-1-DDR-1 signaling is a new important axis involved in malignant potential prostate cancer associated with hormone-refractory status. (PMID:17970783)
• There are significantly higher number of invading cells in DDR1a expressing hepatocellular carcinoma cells. (PMID:17982627)
• DDR2 was differentially upregulated in nasopharyngeal carcinoma and modulated by EBV Zta protein (PMID:18023033)
• The identification of DDR1 dimers provides new insights into the molecular structure of receptor tyrosine kinases and suggests distinct signaling mechanisms of each receptor subfamily. (PMID:18065762)
• KIBRA interacts with discoidin domain receptor 1 to modulate collagen-induced signalling. (PMID:18190796)
• Initiation of the signal requires two collagen receptors, alpha2beta1 integrin and discoidin domain receptor (DDR). Each receptor propagates signals through separate pathways that converge to up-regulate N-cadherin. (PMID:18362184)
• Differentiation of a human oligodendroglial cell line, HOG16, was associated with an increase in mRNA expression of DDR1 and several myelin proteins but not other proteins. DDR1 is upregulated when oligodendrocyte myelinating machinery is activated. (PMID:18836851)
• transfection of the vector encoding full-length DDR1 or siRNA targeting DDR1 up- or downregulated respectively secretion of MMP-2 and -9, and cell invasion (PMID:19262089)
• The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin IIA. (PMID:19401332)
• acts as a costimulatory receptor in T-cell activation (PMID:19752756)
• We failed to show a strong association between the DDR1 gene SNPs and NSV. These facts indicate that there is no genetic association between DDR1 and NSV. (PMID:20007060)
• Type I collagen induces smooth muscle cell migration through DDR1 (PMID:20093046)
• we propose DDR1 as a susceptibility gene for vitiligo, possibly implicating a defective cell adhesion in vitiligo pathogenesis (PMID:20182441)
• Astaxanthin attenuates the UVA-induced up-regulation of matrix-metalloproteinase-1 and skin fibroblast elastase in human dermal fibroblasts (PMID:20219323)
• Results suggest that DDR1 can represent an additional receptor regulating T cell movement in the tissues. (PMID:20353877)
• results suggest that the discoidin domain receptor 1 gene is associated with increased susceptibility, pathological advancement, and the development of proteinuria in childhood IgA nephropathy. (PMID:20372823)
• These observations suggest that DDR1 could be an important constituent of myelin. (PMID:20380825)
• up-regulation of DDR1 may contribute to the progression and poor prognosis of NSCLC and this effect may be associated with increased invasiveness. (PMID:20596615)
• Decreased expression of miR-199a-5p contributes to increased cell invasion by functional deregulation of DDR1 activity in hepatocellular carcinoma. (PMID:20799954)
• These data suggest that extracellular matrix signalling via DDR1 regulates aspects of bronchial epithelial repair, integrity and MMP expression in the airways. (PMID:20884741)
• MMTR is an intrinsic negative cell cycle regulator that modulates the CAK kinase activity via interaction with MAT1. (PMID:20920467)
• Discoidin domain receptor 1 transmembrane signalling, collagen binding and receptor activation occurred with triple-helical peptides containing the GVMGFO motif (PMID:21044884)
• Data show that DDR1 coordinates the Par3/Par6 cell-polarity complex through its carboxy terminus, binding PDZ domains in Par3 and Par6. (PMID:21170030)
• 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)
• These data elucidate DDR1 function pertinent to cirrhosis and indicate the importance of epithelial cell-collagen interactions in chronic liver injury. (PMID:21356365)
• The DDR1 mediates MMP-2 and -9 secretions and invasion induced by native type IV collagen in MDA-MB-231 breast cancer cells. (PMID:21461859)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddr1	ENSDARG00000078523
mus_musculus	Ddr1	ENSMUSG00000003534
rattus_norvegicus	Ddr1	ENSRNOG00000057125

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), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078)

Protein

Protein identifiers

Epithelial discoidin domain-containing receptor 1 — Q08345 (reviewed: Q08345)

Alternative names: CD167 antigen-like family member A, Cell adhesion kinase, Discoidin receptor tyrosine kinase, HGK2, Mammary carcinoma kinase 10, Protein-tyrosine kinase 3A, Protein-tyrosine kinase RTK-6, TRK E, Tyrosine kinase DDR, Tyrosine-protein kinase CAK

All UniProt accessions (33): A0A024RCQ1, A0A0A0MSX3, A2ABL0, A2ABL2, A2ABM8, D6R9C4, D6RAJ3, D6RB35, D6RB82, D6RBU7, D6RGW5, E7EN94, E7ENJ2, E7EPH4, E7EPN2, E7EQ23, E7EQ30, E7ERI6, E7ERN0, E7ES06, E7ESR9, E7ETI3, E7ETX3, E7EUD5, E7EUP7, E7EVT1, E7EVW6, E7EX99, E7EXB0, Q08345, H0Y717, H0Y9F4, H0YAH6

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing. Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11.

Subunit / interactions. Homodimer. Interacts (via PPxY motif) with WWC1 (via WW domains) in a collagen-regulated manner. Forms a tripartite complex with WWC1 and PRKCZ, but predominantly in the absence of collagen. Interacts (tyrosine phosphorylated) with SHC1. Interacts with SRC. Interacts with MYH9. Interacts with CDH1. Interacts with PTPN11. Interacts with NCK2.

Subcellular location. Cell membrane Cell membrane Secreted Cell membrane.

Tissue specificity. Detected in T-47D, MDA-MB-175 and HBL-100 breast carcinoma cells, A-431 epidermoid carcinoma cells, SW48 and SNU-C2B colon carcinoma cells and Hs 294T melanoma cells (at protein level). Expressed at low levels in most adult tissues and is highest in the brain, lung, placenta and kidney. Lower levels of expression are detected in melanocytes, heart, liver, skeletal muscle and pancreas. Abundant in breast carcinoma cell lines. In the colonic mucosa, expressed in epithelia but not in the connective tissue of the lamina propria. In the thyroid gland, expressed in the epithelium of the thyroid follicles. In pancreas, expressed in the islets of Langerhans cells, but not in the surrounding epithelial cells of the exocrine pancreas. In kidney, expressed in the epithelia of the distal tubules. Not expressed in connective tissue, endothelial cells, adipose tissue, muscle cells or cells of hematopoietic origin.

Post-translational modifications. Autophosphorylated in response to fibrillar collagen binding. Glycosylation of Asn-211, but apparently not of Asn-260 or Asn-394, prevents autophosphorylation from occurring in the absence of collagen.

Activity regulation. Inhibited by the multi-targeted cancer drugs imatinib and ponatinib.

Domain organisation. The Gly/Pro-rich domains may be required for an unusual geometry of interaction with ligand or substrates.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q08345-1	1, CAK I, DDR1b	yes
Q08345-2	2, CAK II, DDR1a, Short
Q08345-4	3, DDR1d
Q08345-5	4
Q08345-6	5

RefSeq proteins (37): NP_001189450, NP_001189451, NP_001189452, NP_001284581, NP_001284582, NP_001284583, NP_001374821, NP_001374822, NP_001374823, NP_001374824, NP_001374825, NP_001374826, NP_001374827, NP_001374828, NP_001374829, NP_001374830, NP_001374831, NP_001374832, NP_001374833, NP_001374834, NP_001374835, NP_001374836, NP_001374837, NP_001374838, NP_001374839, NP_001374840, NP_001374841, NP_001374842, NP_001374843, NP_001374844, NP_001374845, NP_001374846, NP_001374847, NP_001397798, NP_001945, NP_054699, NP_054700 (=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 (134 total): strand 38, helix 24, mutagenesis site 12, binding site 11, modified residue 8, sequence variant 7, turn 5, splice variant 5, sequence conflict 5, glycosylation site 4, disulfide bond 3, topological domain 2, domain 2, region of interest 2, signal peptide 1, chain 1, compositionally biased region 1, active site 1, transmembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

34 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6FEX	X-RAY DIFFRACTION	1.29
6FEW	X-RAY DIFFRACTION	1.44
5SB1	X-RAY DIFFRACTION	1.53
5SB2	X-RAY DIFFRACTION	1.6
5SAW	X-RAY DIFFRACTION	1.6
7FEH	X-RAY DIFFRACTION	1.61
6FIN	X-RAY DIFFRACTION	1.67
4BKJ	X-RAY DIFFRACTION	1.7
6FIL	X-RAY DIFFRACTION	1.73
5SAV	X-RAY DIFFRACTION	1.76
6FIQ	X-RAY DIFFRACTION	1.79
5SAU	X-RAY DIFFRACTION	1.8
5SAZ	X-RAY DIFFRACTION	1.8
7BE6	X-RAY DIFFRACTION	1.87
5SAX	X-RAY DIFFRACTION	1.9
3ZOS	X-RAY DIFFRACTION	1.92
5BVW	X-RAY DIFFRACTION	1.94
6HP9	X-RAY DIFFRACTION	1.96
5SB0	X-RAY DIFFRACTION	1.97
5BVO	X-RAY DIFFRACTION	1.98
6FIO	X-RAY DIFFRACTION	1.99
6GWR	X-RAY DIFFRACTION	2.07
5SAY	X-RAY DIFFRACTION	2.19
4CKR	X-RAY DIFFRACTION	2.2
5BVN	X-RAY DIFFRACTION	2.21
6BRJ	X-RAY DIFFRACTION	2.23
5FDP	X-RAY DIFFRACTION	2.25
5BVK	X-RAY DIFFRACTION	2.29
7BCM	X-RAY DIFFRACTION	2.3
6Y23	X-RAY DIFFRACTION	2.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08345-F1	77.27	0.55

Antibody-complex structures (SAbDab): 2 — 4AG4, 8PE9

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): 766 (proton acceptor)

Ligand- & substrate-binding residues (11): 211; 230; 230; 233; 235; 253; 255; 360; 361; 616–624; 655

Post-translational modifications (8): 484, 513, 520, 631, 740, 792, 796, 797

Disulfide bonds (3): 31–185, 74–177, 303–348

Glycosylation sites (4): 211, 260, 370, 394

Mutagenesis-validated functional residues (12):

Position	Phenotype
105	inhibits collagen-induced phosphorylation.
211	phosphorylates regardless of collagen presence, collagen addition does not alter significantly the levels of constitutiv
211	sustained phosphorylation regardless of collagen presence, collagen addition does not alter significantly the levels of
213	phosphorylates regardless of collagen presence, collagen addition does not alter significantly the levels of constitutiv
260	phosphorylates in response to collagen, but at lower levels compared to wild-type. no activation in the absence of colla
371	phosphorylates in response to collagen, but at lower levels compared to wild-type. no activation in the absence of colla
379	phosphorylates in response to collagen, but at lower levels compared to wild-type. phosphorylates in response to collage
393	phosphorylates in response to collagen, but at lower levels compared to wild-type. phosphorylates in response to collage
394	phosphorylates in response to collagen, but at lower levels compared to wild-type. no activation in the absence of colla
655	loss of kinase activity. complete loss of the collagen-independent constitutive activation; when associated with q-211.
707	confers over 20-fold resistance to the ability of an inhibitor to inhibit autophosphorylation.
740	abolishes interaction with ptpn11.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 357 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, CREL_01, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, TAATAAT_MIR126, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_GLAND_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_MAMMARY_GLAND_EPITHELIUM_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_GROWTH, AREB6_01

GO Biological Process (24): regulation of cell growth (GO:0001558), regulation of cell-matrix adhesion (GO:0001952), cell adhesion (GO:0007155), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), embryo implantation (GO:0007566), lactation (GO:0007595), cell population proliferation (GO:0008283), negative regulation of cell population proliferation (GO:0008285), regulation of extracellular matrix disassembly (GO:0010715), positive regulation of neuron projection development (GO:0010976), smooth muscle cell migration (GO:0014909), collagen-activated tyrosine kinase receptor signaling pathway (GO:0038063), peptidyl-tyrosine autophosphorylation (GO:0038083), ear development (GO:0043583), wound healing, spreading of cells (GO:0044319), protein autophosphorylation (GO:0046777), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), branching involved in mammary gland duct morphogenesis (GO:0060444), mammary gland alveolus development (GO:0060749), smooth muscle cell-matrix adhesion (GO:0061302), axon development (GO:0061564), neuron projection extension (GO:1990138), protein phosphorylation (GO:0006468), female pregnancy (GO:0007565)

GO Molecular Function (11): transmembrane receptor protein tyrosine kinase activity (GO:0004714), collagen binding (GO:0005518), ATP binding (GO:0005524), protein tyrosine kinase collagen receptor activity (GO:0038062), metal ion binding (GO:0046872), 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): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), extracellular exosome (GO:0070062), extracellular region (GO:0005576), 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
cell-matrix adhesion	2
cellular process	2
cellular anatomical structure	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
regulation of cell-substrate adhesion	1
enzyme-linked receptor protein signaling pathway	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
extracellular matrix disassembly	1
regulation of extracellular matrix organization	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
muscle cell migration	1
cell surface receptor protein tyrosine kinase signaling pathway	1
collagen-activated signaling pathway	1
peptidyl-tyrosine phosphorylation	1
protein autophosphorylation	1
sensory organ development	1
cell migration	1
epiboly involved in wound healing	1
protein phosphorylation	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
branching morphogenesis of an epithelial tube	1
mammary gland duct morphogenesis	1
anatomical structure development	1
mammary gland lobule development	1
protein tyrosine kinase activity	1
transmembrane receptor protein kinase activity	1

Protein interactions and networks

STRING

1320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDR1	TM4SF1	P30408	862
DDR1	COL3A1	P02461	743
DDR1	COL1A1	P02452	711
DDR1	COL5A1	P20908	704
DDR1	SDCBP2	Q9H190	660
DDR1	COL4A1	P02462	646
DDR1	CD9	P21926	629
DDR1	CDH1	P12830	609
DDR1	ITGA2	P17301	591
DDR1	PRKCA	P17252	589
DDR1	MMP9	P14780	559
DDR1	GP6	Q9HCN6	531
DDR1	WWC1	Q8IX03	529
DDR1	COL11A1	P12107	517
DDR1	AKT1	P31749	504

IntAct

94 interactions, top by confidence:

A	B	Type	Score
	DDR1	psi-mi:“MI:2364”(proximity)	0.670
DDR2	DDR1	psi-mi:“MI:0915”(physical association)	0.620
DDR1	PTPN11	psi-mi:“MI:0915”(physical association)	0.580
PTPN11	DDR1	psi-mi:“MI:0915”(physical association)	0.580
NCK2	DDR1	psi-mi:“MI:0915”(physical association)	0.580
DDR1	NCK2	psi-mi:“MI:0915”(physical association)	0.580
PTPN11	DDR1	psi-mi:“MI:0914”(association)	0.580
DDR1	RGS2	psi-mi:“MI:0915”(physical association)	0.550
	XPO1	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
EPHA2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
MRAP2	PODXL	psi-mi:“MI:0914”(association)	0.530
DLK1	SCAMP3	psi-mi:“MI:0914”(association)	0.530
ITM2A	NDUFB5	psi-mi:“MI:0914”(association)	0.530
TMEM200A	STX6	psi-mi:“MI:0914”(association)	0.530
MANSC1	SMPD2	psi-mi:“MI:0914”(association)	0.530
EVA1B	NRP1	psi-mi:“MI:0914”(association)	0.530
	DDR1	psi-mi:“MI:0915”(physical association)	0.500
DDR1	COL3A1	psi-mi:“MI:0407”(direct interaction)	0.440
	DDR1	psi-mi:“MI:0915”(physical association)	0.400
DDR1	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
DDR1	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350

BioGRID (138): DDR1 (Affinity Capture-RNA), DDR1 (Affinity Capture-RNA), CDH1 (Affinity Capture-Western), CDH2 (Affinity Capture-Western), DDR1 (Affinity Capture-MS), DDR1 (Affinity Capture-MS), DDR1 (Affinity Capture-RNA), TK1 (Negative Genetic), MAP3K10 (Negative Genetic), PIM1 (Positive Genetic), DDR1 (Affinity Capture-MS), DDR1 (PCA), SNRNP40 (Two-hybrid), DDR1 (Two-hybrid), DDR1 (Two-hybrid)

ESM2 similar proteins: A0A0U1RPR8, O02740, O08644, O09127, O15197, O19179, O73875, O73878, P0C0K6, P0C0K7, P14616, P16067, P20594, P21709, P26770, P29317, P29322, P35590, P46197, P51839, P51840, P51841, P51842, P52333, P52785, P54753, P54754, P54760, P54761, P55203, P55205, Q02846, Q03146, Q06805, Q06806, Q08345, Q1KL86, Q5JZY3, Q5SDA5, Q60750

Diamond homologs: A0M8R7, A0M8S8, A1X150, B3MH43, B3NS99, B4GBH0, B4HNW4, B4KPU0, B4MR28, B4P5Q9, B4QC63, O15146, O73798, P00529, P04629, P06213, P08069, P08581, P08922, P08941, P09208, P14616, P14617, P15127, P15208, P15209, P16056, P23049, P24062, P24786, P35739, P42159, P42681, P97523, Q00PJ8, Q01973, Q03146, Q03351, Q04912, Q05688

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
DDR1	“up-regulates activity”	DDR1	phosphorylation
COL1A1	“up-regulates activity”	DDR1	binding
COL21A1	“up-regulates activity”	DDR1	binding
DDR1	“up-regulates quantity by expression”	CXCL5	“transcriptional regulation”
COL1A1	up-regulates	DDR1	binding
DDR1	“up-regulates activity”	TM4SF1	binding
DDR1	“up-regulates activity”	PTPN11	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 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
EPH-Ephrin signaling	5	12.9×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	6	22.2×	2e-04
T cell costimulation	5	20.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	104
Likely benign	16
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2997 predictions. Top by Δscore:

Variant	Effect	Δscore
6:30888686:A:AG	acceptor_gain	1.0000
6:30888687:G:GG	acceptor_gain	1.0000
6:30888687:GA:G	acceptor_gain	1.0000
6:30888773:TGGC:T	donor_gain	1.0000
6:30888906:A:AG	acceptor_gain	1.0000
6:30888907:G:GG	acceptor_gain	1.0000
6:30888907:GCCAA:G	acceptor_gain	1.0000
6:30889428:G:GT	donor_gain	1.0000
6:30890963:T:A	acceptor_gain	1.0000
6:30890969:ACAG:A	acceptor_gain	1.0000
6:30890970:CA:C	acceptor_loss	1.0000
6:30890971:A:AG	acceptor_gain	1.0000
6:30890971:AG:A	acceptor_gain	1.0000
6:30890971:AGGT:A	acceptor_gain	1.0000
6:30890972:G:GG	acceptor_gain	1.0000
6:30890972:GG:G	acceptor_gain	1.0000
6:30890972:GGT:G	acceptor_gain	1.0000
6:30890972:GGTG:G	acceptor_gain	1.0000
6:30890972:GGTGA:G	acceptor_gain	1.0000
6:30891116:GAGGG:G	donor_gain	1.0000
6:30891117:AGGG:A	donor_gain	1.0000
6:30891118:GGG:G	donor_gain	1.0000
6:30891118:GGGG:G	donor_gain	1.0000
6:30891119:GG:G	donor_gain	1.0000
6:30891119:GGG:G	donor_gain	1.0000
6:30891120:GG:G	donor_gain	1.0000
6:30891121:G:GG	donor_gain	1.0000
6:30891375:CCCAG:C	acceptor_loss	1.0000
6:30891378:A:AG	acceptor_gain	1.0000
6:30891378:AGA:A	acceptor_loss	1.0000

AlphaMissense

5909 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:30889230:T:A	W73R	1.000
6:30889230:T:C	W73R	1.000
6:30889232:G:C	W73C	1.000
6:30889232:G:T	W73C	1.000
6:30896845:G:C	G617R	1.000
6:30896845:G:T	G617C	1.000
6:30896846:G:A	G617D	1.000
6:30896846:G:T	G617V	1.000
6:30896851:G:C	G619R	1.000
6:30896851:G:T	G619C	1.000
6:30896852:G:A	G619D	1.000
6:30896852:G:T	G619V	1.000
6:30896857:T:A	F621I	1.000
6:30896857:T:C	F621L	1.000
6:30896857:T:G	F621V	1.000
6:30896858:T:C	F621S	1.000
6:30896858:T:G	F621C	1.000
6:30896859:T:A	F621L	1.000
6:30896859:T:G	F621L	1.000
6:30896860:G:A	G622R	1.000
6:30896860:G:C	G622R	1.000
6:30896860:G:T	G622W	1.000
6:30896861:G:A	G622E	1.000
6:30896861:G:T	G622V	1.000
6:30897021:T:C	L626P	1.000
6:30897102:C:A	A653D	1.000
6:30897105:T:A	V654D	1.000
6:30897107:A:G	K655E	1.000
6:30897109:G:C	K655N	1.000
6:30897109:G:T	K655N	1.000

dbSNP variants (sampled 300 via entrez): RS1000211044 (6:30894019 G>A), RS1000297916 (6:30902381 G>A), RS1000362602 (6:30887088 C>T), RS1000405774 (6:30879506 A>C,G), RS1000561827 (6:30903700 C>G), RS1000727843 (6:30885467 C>G), RS1000735660 (6:30902760 T>C), RS1000742491 (6:30896653 C>T), RS1000797381 (6:30887419 C>T), RS1000890964 (6:30890762 G>A), RS1001098018 (6:30885079 A>T), RS1001121660 (6:30884094 C>T), RS1001165797 (6:30899484 A>G), RS1001215472 (6:30883257 C>T), RS1001393100 (6:30888940 C>A,G,T)

Disease associations

OMIM: gene MIM:600408 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
chondrodysplasia	Limited	Autosomal recessive

Mondo (2): breast ductal adenocarcinoma (MONDO:0005590), chondrodysplasia (MONDO:0022723)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST000549_35	HIV-1 control	1.000000e-06
GCST000853_3	Ulcerative colitis	4.000000e-06
GCST001884_6	Age-related macular degeneration	2.000000e-11
GCST002876_2	Type 1 diabetes and autoimmune thyroid diseases	3.000000e-14
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_121	Autism spectrum disorder or schizophrenia	3.000000e-13
GCST004521_131	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_132	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_171	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_19	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_2	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_210	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_27	Autism spectrum disorder or schizophrenia	1.000000e-09
GCST004521_295	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_3	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_33	Autism spectrum disorder or schizophrenia	1.000000e-08
GCST004521_48	Autism spectrum disorder or schizophrenia	1.000000e-09
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_79	Autism spectrum disorder or schizophrenia	1.000000e-16
GCST004748_104	Lung cancer	7.000000e-19
GCST004749_1	Lung cancer in ever smokers	2.000000e-13
GCST005541_13	Sarcoidosis (Lofgren’s syndrome vs non-Lofgren’s syndrome)	1.000000e-25
GCST005606_4	Response to hepatitis B vaccine	2.000000e-06
GCST005790_56	Rosacea symptom severity	1.000000e-07
GCST006575_32	Takayasu arteritis	1.000000e-06
GCST007201_374	Schizophrenia	3.000000e-19

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0004645	response to vaccine
EFO:0009180	rosacea severity measurement
EFO:0004517	arterial stiffness measurement
EFO:0005670	smoking initiation
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4742292 (PROTEIN-PROTEIN INTERACTION), CHEMBL5319 (SINGLE PROTEIN), CHEMBL6195681 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

77 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 519,259 (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
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2035187	PACRITINIB	4	3,345
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
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL576982	QUIZARTINIB	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL941	IMATINIB	4
CHEMBL101253	VATALANIB	3
CHEMBL1908391	MASITINIB	3
CHEMBL217092	SARACATINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL270995	BRIVANIB ALANINATE	3
CHEMBL31965	CANERTINIB	3

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 (15 total), top 15:

Ligand	Action	Affinity	Parameter
mAb PRTH-101	Inhibition	9.41	pKd
merestinib	Inhibition	9.02	pKd
naporafenib	Inhibition	8.74	pKd
compound 7k [PMID: 23521020]	Inhibition	8.64	pIC50
compound 4 [PMID: 26191369]	Inhibition	8.48	pIC50
DDR1 inhibitor 7rh	Inhibition	8.17	pIC50
DDR1/2 inhibitor 5n	Inhibition	8.03	pIC50
compound 6j [PMID: 27219676]	Inhibition	8.03	pIC50
compound 1 [PMID: 31477924]	Inhibition	8.0	pIC50
RIPK1 inhibitor 22b	Inhibition	7.46	pIC50
nilotinib	Inhibition	7.37	pIC50
NVP-BHG712 isomer	Inhibition	7.07	pKd
DDR-IN-1	Inhibition	6.98	pIC50
CHMFL-KIT-64	Inhibition	6.87	pIC50
imatinib	Inhibition	6.47	pIC50

Binding affinities (BindingDB)

1171 measured of 1198 human assays (1198 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
5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one	KD	2.8 nM
3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-[[(3S)-3-(methylaminomethyl)pyrrolidin-1-yl]methyl]-5-(trifluoromethyl)benzamide	IC50	4.6 nM	US-9695118: Benzamide derivative
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
4-[[(3S)-3-aminopiperidin-1-yl]methyl]-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-3-(trifluoromethoxy)benzamide	IC50	6.5 nM	US-9695118: Benzamide derivative
3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-[[(3S)-3-(methylamino)piperidin-1-yl]methyl]-5-(trifluoromethyl)benzamide	IC50	6.7 nM	US-9695118: Benzamide derivative
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
4-[[(3S)-3-aminopiperidin-1-yl]methyl]-3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-5-(trifluoromethyl)benzamide	IC50	7.4 nM	US-9695118: Benzamide derivative
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
7-((R)-3-Amino-pyrrolidin-1-ylmethyl)-3-(5-chloro-2-ethanesulfonyl-benzyl)-6-trifluoromethyl-1 H-quinazoline-2,4-dione	IC50	7.9 nM	US-9567304: Quinazolinedione derivative
(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-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide	IC50	9 nM	US-20250177391: INHIBITORS OF DDR1 AND DDR2 FOR THE TREATMENT OF ARTHRITIS
N’-(2-ethylsulfanyl-5-fluorophenyl)-3-(trifluoromethyl)benzohydrazide	IC50	9 nM	US-9695118: Benzamide derivative
3-chloro-N-[(5-chloro-2-ethylsulfonyl-3-methylphenyl)methyl]-4-[[(3S)-3-(methylamino)piperidin-1-yl]methyl]-5-(trifluoromethyl)benzamide	IC50	9.1 nM	US-9695118: Benzamide derivative
4-[[(3S)-3-aminopiperidin-1-yl]methyl]-3-bromo-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-5-(trifluoromethyl)benzamide	IC50	9.2 nM	US-9695118: Benzamide derivative
N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzamide	IC50	9.7 nM	US-9695118: Benzamide derivative
4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole	KD	9.8 nM
7-((R)-3-Amino-pyrrolidin-1-ylmethyl)-8-bromo-3-(5-chloro-2-ethanesulfonyl-benzyl)-6-trifluoromethyl-1H-quinazoline-2,4-dione	IC50	9.8 nM	US-9567304: Quinazolinedione derivative
3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-[[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-5-(trifluoromethyl)benzamide	IC50	9.9 nM	US-9695118: Benzamide derivative
4-[[(3R)-3-aminopiperidin-1-yl]methyl]-3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-5-(trifluoromethyl)benzamide	IC50	9.9 nM	US-9695118: Benzamide derivative
3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-[[(3R)-3-(methylamino)piperidin-1-yl]methyl]-5-(trifluoromethyl)benzamide	IC50	9.9 nM	US-9695118: Benzamide derivative
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
4-[[(3R)-3-aminopyrrolidin-1-yl]methyl]-3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-5-(trifluoromethyl)benzamide	IC50	10 nM	US-9695118: Benzamide derivative
3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-[[(3S)-3-(dimethylamino)piperidin-1-yl]methyl]-5-(trifluoromethyl)benzamide	IC50	10 nM	US-9695118: Benzamide derivative
4-[[(3S)-3-(aminomethyl)pyrrolidin-1-yl]methyl]-3-bromo-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-5-(trifluoromethyl)benzamide	IC50	10 nM	US-9695118: Benzamide derivative
3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-(5-oxa-2,8-diazaspiro[3.5]nonan-8-ylmethyl)-5-(trifluoromethyl)benzamide	IC50	10 nM	US-9695118: Benzamide derivative
3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-(1,8-diazaspiro[5.5]undecan-8-ylmethyl)-5-(trifluoromethyl)benzamide	IC50	10 nM	US-9695118: Benzamide derivative
4-[[(3S)-3-(aminomethyl)pyrrolidin-1-yl]methyl]-3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-5-(trifluoromethyl)benzamide	IC50	10 nM	US-9695118: Benzamide derivative
3-bromo-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-[[(3S)-3-(methylaminomethyl)pyrrolidin-1-yl]methyl]-5-(trifluoromethyl)benzamide	IC50	10 nM	US-9695118: Benzamide derivative
2-[8-(2,3,3a,4,5,6,7,7a-octahydro-1H-indazole-5-carbonyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl]-N-phenylacetamide	IC50	10.6 nM	US-10239876: Triaza-spirodecanones as DDR1 inhibitors
(rac, trans)-2-(8-(1H-Indazole-5-carbonyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)-N-(2-phenylcyclopropyl)acetamide	IC50	10.9 nM	US-10239876: Triaza-spirodecanones as DDR1 inhibitors
3-[(5-chloro-2-ethylsulfonylphenyl)methyl]-7-[[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-6-(trifluoromethyl)-1H-quinazoline-2,4-dione	IC50	11 nM	US-9567304: Quinazolinedione derivative
8-chloro-3-[(5-chloro-2-ethylsulfonylphenyl)methyl]-7-[[(3S)-3-(methylaminomethyl)pyrrolidin-1-yl]methyl]-6-(trifluoromethyl)quinazolin-4-one	IC50	11 nM	US-10005739: Quinazolinone and isoquinolinone derivative
4-[[(3S)-3-(2-aminoethylamino)piperidin-1-yl]methyl]-3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-5-(trifluoromethyl)benzamide	IC50	11 nM	US-9695118: Benzamide derivative
3-chloro-N-[(2-ethylsulfonyl-5-methylphenyl)methyl]-4-[[(3S)-3-(methylamino)piperidin-1-yl]methyl]-5-(trifluoromethyl)benzamide	IC50	11 nM	US-9695118: Benzamide derivative
3-chloro-N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-[[(3R)-3-(methylamino)pyrrolidin-1-yl]methyl]-5-(trifluoromethyl)benzamide	IC50	11 nM	US-9695118: Benzamide derivative
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
7-((S)-3-Aminomethyl-pyrrolidin-1-ylmethyl)-8-bromo-3-(5-chloro-2-ethanesulfonyl-benzyl)-6-trifluoromethyl-1H-quinazoline-2,4-dione	IC50	12 nM	US-9567304: Quinazolinedione derivative
7-((R)-3-Amino-pyrrolidin-1-ylmethyl)-6-bromo-3-(5-chloro-2-ethanesulfonyl-benzyl)-1H-quinazoline-2,4-dione	IC50	12 nM	US-9567304: Quinazolinedione derivative
7-((S)-3- Aminomethyl- pyrrolidin-1- ylmethyl)-6-bromo- 3-(5-chloro-2- ethanesulfonyl- benzyl)-1H- quinazoline-2,4- dione	IC50	12 nM	US-9567304: Quinazolinedione derivative
8-chloro-3-(5-chloro-2-ethylsulfonylanilino)-6-(trifluoromethyl)quinazolin-4-one	IC50	12 nM	US-10005739: Quinazolinone and isoquinolinone derivative
N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzamide	IC50	12 nM	US-9695118: Benzamide derivative
N-[(5-chloro-2-ethylsulfonylphenyl)methyl]-4-[[(3S)-3-(methylamino)piperidin-1-yl]methyl]-3-(trifluoromethyl)benzamide	IC50	12 nM	US-9695118: Benzamide derivative

ChEMBL bioactivities

1809 potent at pChembl≥5 of 1837 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	Kd	0.2	nM	FORETINIB
9.40	Kd	0.4	nM	BAY-826
9.30	IC50	0.5	nM	DASATINIB
9.22	Kd	0.6	nM	CHEMBL2336015
9.16	Kd	0.69	nM	AST-487
9.16	Kd	0.69	nM	DASATINIB
9.15	IC50	0.7078	nM	CHEMBL4539920
9.15	Kd	0.7	nM	IMATINIB
9.10	Kd	0.7943	nM	IMATINIB
9.05	IC50	0.9	nM	BAY-826
8.96	Kd	1.1	nM	NILOTINIB
8.86	IC50	1.393	nM	CHEMBL3421914
8.82	Kd	1.5	nM	SORAFENIB
8.82	EC50	1.5	nM	BAY-826
8.77	Kd	1.7	nM	CEDIRANIB
8.74	Kd	1.8	nM	NAPORAFENIB
8.72	Kd	1.9	nM	DORAMAPIMOD
8.70	IC50	2	nM	CHEMBL3969260
8.68	IC50	2.09	nM	STAUROSPORINE
8.68	Kd	2.1	nM	BAY-309
8.66	Kd	2.2	nM	CHEMBL4097012
8.66	Kd	2.2	nM	CHEMBL4559959
8.65	IC50	2.26	nM	CHEMBL5560252
8.64	IC50	2.29	nM	CHEMBL2336037
8.62	IC50	2.4	nM	CHEMBL4161036
8.62	Kd	2.4	nM	CHEMBL386051
8.52	Kd	3	nM	CHEMBL400402
8.52	IC50	3	nM	CHEMBL4466555
8.52	IC50	3	nM	CHEMBL6189164
8.49	IC50	3.2	nM	CHEMBL4175086
8.47	Kd	3.4	nM	CHEMBL2148124
8.44	IC50	3.65	nM	STAUROSPORINE
8.43	IC50	3.7	nM	NILOTINIB
8.41	IC50	3.9	nM	CHEMBL4164448
8.41	IC50	3.9	nM	CHEMBL4164030
8.40	IC50	3.97	nM	CHEMBL4439970
8.40	IC50	4	nM	CHEMBL4787515
8.39	IC50	4.04	nM	CHEMBL2336040
8.37	IC50	4.28	nM	STAUROSPORINE
8.36	IC50	4.4	nM	CHEMBL4846921
8.34	IC50	4.6	nM	CHEMBL6055733
8.33	IC50	4.7	nM	CHEMBL3797933
8.33	IC50	4.67	nM	CHEMBL4539920
8.33	Kd	4.7	nM	CHEMBL4553037
8.32	IC50	4.8	nM	DASATINIB
8.32	IC50	4.799	nM	CHEMBL552425
8.30	IC50	5	nM	CHEMBL3944137
8.30	Kd	5	nM	GOLVATINIB
8.30	IC50	5	nM	CHEMBL4174682
8.30	IC50	5	nM	CHEMBL4794765

PubChem BioAssay actives

453 with measured affinity, of 1128 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
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	1202714: Binding affinity to DDR1 (unknown origin)	kd	0.0002	uM
3-cyano-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	2155084: Binding affinity to DDR1 (unknown origin) assessed as dissociation constant by KINOME scan assay	kd	0.0004	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	1202712: Inhibition of DDR1b (unknown origin) assessed as reduction in collagen-induced DDR1b activation	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	732851: Binding affinity to DDR1 ATP binding site (unknown origin) after 1 hr by competitive binding assay	kd	0.0006	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435400: Binding constant for DDR1 kinase domain	kd	0.0007	uM
4-fluoro-3-[[5-(1-methylpyrazol-3-yl)-3-pyridinyl]methylamino]-N-[3-(trifluoromethoxy)phenyl]benzamide	1541783: Inhibition of FLAG-tagged DDR1 in human HEK293 cells assessed as reduction in collagen-1-induced DDR1 phosphorylation incubated for 18 hrs by ELISA	ic50	0.0007	uM
Imatinib	435400: Binding constant for DDR1 kinase domain	kd	0.0007	uM
Nilotinib	624850: Binding constant for DDR1 kinase domain	kd	0.0011	uM
Sorafenib	1202714: Binding affinity to DDR1 (unknown origin)	kd	0.0015	uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	624850: Binding constant for DDR1 kinase domain	kd	0.0017	uM
N-[3-[2-(2-hydroxyethoxy)-6-morpholin-4-yl-4-pyridinyl]-4-methylphenyl]-2-(trifluoromethyl)pyridine-4-carboxamide	1545549: Binding affinity to wild-type human partial length DDR1 (R565 to V876 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0018	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	1202714: Binding affinity to DDR1 (unknown origin)	kd	0.0019	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	1715381: Inhibition of human DDR1 using KKSRGDYMTMQIG as substrate by [gamma-33P]-ATP assay	ic50	0.0021	uM
(4R)-4-methyl-N-[3-[(4-methyl-1,4-diazepan-1-yl)methyl]-5-(trifluoromethyl)phenyl]-2-pyrimidin-5-yl-3,4-dihydro-1H-isoquinoline-7-carboxamide	1460467: Binding affinity to human DNA-tagged DDR1 expressed in bacterial expression system measured after 1 hr by quantitative PCR analysis	kd	0.0022	uM
4-ethyl-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-3-(3-pyrazolo[1,5-a]pyrimidin-6-ylphenyl)benzamide	2074639: Binding affinity to DDR1 (unknown origin) assessed as dissociation constant	kd	0.0022	uM
2-morpholin-4-ylethyl 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	0.0023	uM
2-morpholin-4-ylethyl 4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]pyrimidin-4-yl]piperazine-1-carboxylate	2074661: Inhibition of DDR1 (unknown origin) using Fluorescein-Poly GAT as substrate by TR-FRET analysis	ic50	0.0023	uM
N-(3-chlorophenyl)-4-methyl-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamide	732858: Inhibition of DDR1 (unknown origin) using fluorescein-labeled poly GAT as substrate incubated for 1 hr prior to substrate addition measured after 1 hr by TR-FRET assay	ic50	0.0023	uM
3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-4-methyl-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]benzamide	1356711: Inhibition of DDR1 (unknown origin) incubated for 1 hr using fluorescein-poly-GAT substrate by TR-FRET based LANCE ULTRA kinase assay	ic50	0.0024	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624850: Binding constant for DDR1 kinase domain	kd	0.0024	uM
2-(dimethylamino)ethyl 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	0.0026	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1424972: 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	0.0030	uM
N-[4-chloro-3-(trifluoromethyl)phenyl]-4-methyl-3-[[1-(7H-purin-6-yl)cyclopropanecarbonyl]amino]benzamide	1534561: Inhibition of human DDR1 using KKSRGDYMTMQIG as substrate by [gamma-33P]-ATP assay	ic50	0.0030	uM
ethyl 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	0.0032	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	0.0032	uM
4-ethyl-3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]benzamide	1356711: Inhibition of DDR1 (unknown origin) incubated for 1 hr using fluorescein-poly-GAT substrate by TR-FRET based LANCE ULTRA kinase assay	ic50	0.0032	uM
4-ethyl-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]benzamide	1356711: Inhibition of DDR1 (unknown origin) incubated for 1 hr using fluorescein-poly-GAT substrate by TR-FRET based LANCE ULTRA kinase assay	ic50	0.0039	uM
3-[2-(2-aminopyrimidin-5-yl)ethynyl]-4-ethyl-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]benzamide	1356711: Inhibition of DDR1 (unknown origin) incubated for 1 hr using fluorescein-poly-GAT substrate by TR-FRET based LANCE ULTRA kinase assay	ic50	0.0039	uM
5-[[2-methyl-5-[[3-(trifluoromethyl)phenyl]carbamoyl]anilino]methyl]pyridine-3-carboxamide	1541770: Inhibition of kinase tracer 178 binding to recombinant human His-tagged DDR1 expressed in baculovirus infected Sf9 cells incubated for 1 hr by TR-FRET based LanthaScreen Eu kinase binding assay	ic50	0.0040	uM
N-(3-methoxyphenyl)-4-methyl-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamide	732858: Inhibition of DDR1 (unknown origin) using fluorescein-labeled poly GAT as substrate incubated for 1 hr prior to substrate addition measured after 1 hr by TR-FRET assay	ic50	0.0040	uM
2-chloroethyl 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	0.0042	uM
methyl 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	0.0043	uM
2-[[6-[4-[(E)-but-2-enoyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-N-(2-chloro-6-methylphenyl)-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	0.0043	uM
N-[3-[2-[4-(4-ethylpiperazin-1-yl)anilino]thieno[3,2-d]pyrimidin-7-yl]phenyl]methanesulfonamide	1779437: Inhibition of DDR1 (unknown origin)	ic50	0.0044	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	0.0045	uM
(4R)-4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-pyrimidin-5-yl-3,4-dihydro-1H-isoquinoline-7-carboxamide	1625886: Binding affinity to wild type human partial length DDR1 (565 to 876 residues) expressed in bacterial expression system preincubated for 1 hr measured after 30 mins by qPCR method	kd	0.0047	uM
5-[2-methyl-5-[[3-(trifluoromethyl)phenyl]carbamoyl]anilino]pyridine-3-carboxamide	1541783: Inhibition of FLAG-tagged DDR1 in human HEK293 cells assessed as reduction in collagen-1-induced DDR1 phosphorylation incubated for 18 hrs by ELISA	ic50	0.0048	uM
4-ethyl-3-[2-[2-(methylamino)pyrimidin-5-yl]ethynyl]-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]benzamide	1356711: Inhibition of DDR1 (unknown origin) incubated for 1 hr using fluorescein-poly-GAT substrate by TR-FRET based LANCE ULTRA kinase assay	ic50	0.0050	uM
1-N’-[2-fluoro-4-[[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]-4-pyridinyl]oxy]phenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	1424972: 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	0.0050	uM
4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamide	1701214: Inhibition of DDR1 (unknown origin) using fluorescein-poly GAT as substrate measured after 1 hr by LANCE ULTRA kinase assay	ic50	0.0050	uM
methyl 3-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]pyrrolidine-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	0.0052	uM
(2R)-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-(pyrimidin-5-ylamino)-2,3-dihydro-1H-indene-5-carboxamide	1608344: Inhibition of GST-tagged recombinant human DDR1 (440 to 876 amino acids) expressed in baculovirus using fluorescein-poly GAT as substrate after 1 hr by FRET-based LanthaScreen Eu kinase binding assay	ic50	0.0056	uM
(2R)-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-[methyl(pyrimidin-5-yl)amino]-2,3-dihydro-1H-indene-5-carboxamide	1608349: Binding affinity to wild-type human partial length DDR1 (R565 to V876 residues) expressed in bacterial expression system	kd	0.0059	uM
3-[(5-methoxy-3-pyridinyl)methylamino]-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide	1541770: Inhibition of kinase tracer 178 binding to recombinant human His-tagged DDR1 expressed in baculovirus infected Sf9 cells incubated for 1 hr by TR-FRET based LanthaScreen Eu kinase binding assay	ic50	0.0059	uM
propan-2-yl 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	0.0060	uM
4-methyl-N-(3-methylphenyl)-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamide	732858: Inhibition of DDR1 (unknown origin) using fluorescein-labeled poly GAT as substrate incubated for 1 hr prior to substrate addition measured after 1 hr by TR-FRET assay	ic50	0.0060	uM
N-[2-methyl-5-[(1S)-1-(phenylcarbamoylamino)ethyl]phenyl]imidazo[1,2-a]pyridine-3-carboxamide	1242618: Inhibition of DDR1 (unknown origin) after 1 hr by time resolved fluorescence method	ic50	0.0060	uM
4-methyl-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)-N-[3-(trifluoromethyl)phenyl]benzamide	732858: Inhibition of DDR1 (unknown origin) using fluorescein-labeled poly GAT as substrate incubated for 1 hr prior to substrate addition measured after 1 hr by TR-FRET assay	ic50	0.0061	uM
4-ethyl-3-(2-imidazo[1,2-a]pyridin-3-ylethynyl)-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]benzamide	1356711: Inhibition of DDR1 (unknown origin) incubated for 1 hr using fluorescein-poly-GAT substrate by TR-FRET based LANCE ULTRA kinase assay	ic50	0.0062	uM
N-(3,5-dimethylphenyl)-4-methyl-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamide	732858: Inhibition of DDR1 (unknown origin) using fluorescein-labeled poly GAT as substrate incubated for 1 hr prior to substrate addition measured after 1 hr by TR-FRET assay	ic50	0.0063	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, decreases methylation, increases abundance, increases expression	7
Valproic Acid	affects expression, affects cotreatment, decreases expression	5
Particulate Matter	increases abundance, affects cotreatment, increases expression, decreases expression	3
bisphenol A	increases expression, decreases methylation	2
trichostatin A	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cisplatin	affects cotreatment, increases expression, affects response to substance	2
Smoke	decreases expression	2
Tretinoin	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
napabucasin	decreases expression	1
testosterone enanthate	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
butyraldehyde	decreases expression	1
cupric chloride	decreases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
cetrorelix	increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrimidifen	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	decreases expression	1
1-(2-chlorobenzyl)-5’-phenyl-3’H-spiro(indoline-3,2’-(1,3,4)thiadiazol)-2-one	decreases expression	1

ChEMBL screening assays

422 unique, capped per target: 422 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4713763	Binding	Protac activity at CRBN/DDR1 in human BxPC-3 cells assessed as DDR1 degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — J Med Chem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1PX	Abcam HeLa DDR1 KO	Cancer cell line	Female
CVCL_B8UP	Abcam MCF-7 DDR1 KO	Cancer cell line	Female
CVCL_E0BK	Ubigene HeLa DDR1 KO	Cancer cell line	Female
CVCL_E6TW	Genomeditech HEK-293 H_DDR1	Transformed cell line	Female
CVCL_SK60	HAP1 DDR1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery