TYRO3

Summary

TYRO3 (TYRO3 protein tyrosine kinase, HGNC:12446) is a protein-coding gene on chromosome 15q15.1, encoding Tyrosine-protein kinase receptor TYRO3 (Q06418). Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6.

The gene is part of a 3-member transmembrane receptor kinase receptor family with a processed pseudogene distal on chromosome 15. The encoded protein is activated by the products of the growth arrest-specific gene 6 and protein S genes and is involved in controlling cell survival and proliferation, spermatogenesis, immunoregulation and phagocytosis. The encoded protein has also been identified as a cell entry factor for Ebola and Marburg viruses.

Source: NCBI Gene 7301 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 136 total
• Druggable target: yes — 30 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006293

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12446
Approved symbol	TYRO3
Name	TYRO3 protein tyrosine kinase
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	Dtk, Brt, Tif, Sky, Etk-2, Rek
Ensembl gene	ENSG00000092445
Ensembl biotype	protein_coding
OMIM	600341
Entrez	7301

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000263798, ENST00000559066, ENST00000559815, ENST00000559851, ENST00000560162, ENST00000560227, ENST00000560992, ENST00000568343, ENST00000568490, ENST00000869538, ENST00000869539, ENST00000869540, ENST00000869541, ENST00000938082, ENST00000938083, ENST00000938084, ENST00000941856, ENST00000941857, ENST00000941858, ENST00000941859

RefSeq mRNA: 2 — MANE Select: NM_006293 NM_001330264, NM_006293

CCDS: CCDS10080, CCDS81866

Canonical transcript exons

ENST00000263798 — 19 exons

Exon	Start	End
ENSE00000586436	41568878	41569022
ENSE00000586447	41570240	41570340
ENSE00000586453	41570604	41570699
ENSE00000586489	41561539	41561639
ENSE00000586496	41564184	41564270
ENSE00000676763	41562548	41562718
ENSE00000676767	41565026	41565141
ENSE00000676806	41568217	41568362
ENSE00000676824	41571038	41571118
ENSE00000676867	41573679	41573815
ENSE00001152503	41577886	41583589
ENSE00001152512	41559212	41559381
ENSE00003466090	41571595	41571687
ENSE00003476947	41573002	41573111
ENSE00003617228	41572443	41572564
ENSE00003625993	41567360	41567537
ENSE00003636584	41570027	41570156
ENSE00003658223	41561127	41561310
ENSE00003683162	41573308	41573467

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2896 / max 166.0870, expressed in 1529 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146197	8.8164	1459
146194	2.5007	953
146195	1.8439	638
146196	0.0709	34
207479	0.0577	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	98.74	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.49	gold quality
paraflocculus	UBERON:0005351	98.31	gold quality
prefrontal cortex	UBERON:0000451	98.01	gold quality
middle frontal gyrus	UBERON:0002702	97.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.64	gold quality
cerebellar cortex	UBERON:0002129	97.60	gold quality
cerebellar hemisphere	UBERON:0002245	97.60	gold quality
right frontal lobe	UBERON:0002810	97.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.27	gold quality
cerebellum	UBERON:0002037	97.02	gold quality
frontal cortex	UBERON:0001870	96.88	gold quality
frontal lobe	UBERON:0016525	96.88	gold quality
cerebellar vermis	UBERON:0004720	96.57	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.45	gold quality
cingulate cortex	UBERON:0003027	96.41	gold quality
anterior cingulate cortex	UBERON:0009835	96.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.37	gold quality
neocortex	UBERON:0001950	96.35	gold quality
left ovary	UBERON:0002119	96.25	gold quality
amygdala	UBERON:0001876	95.90	gold quality
spinal cord	UBERON:0002240	95.84	gold quality
cerebral cortex	UBERON:0000956	95.48	gold quality
right ovary	UBERON:0002118	95.42	gold quality
postcentral gyrus	UBERON:0002581	95.05	gold quality
temporal lobe	UBERON:0001871	95.04	gold quality
telencephalon	UBERON:0001893	94.86	gold quality
corpus callosum	UBERON:0002336	94.73	gold quality
superior frontal gyrus	UBERON:0002661	94.70	gold quality
parietal lobe	UBERON:0001872	94.60	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	895.69
E-ENAD-27	yes	68.10
E-HCAD-10	yes	17.99
E-ANND-3	yes	5.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT3B

Literature-anchored findings (GeneRIF, showing 40)

• Gas6 receptors were not upregulated in any of the allograft groups, except for the Axl receptor, which increased only in acute tubular necrosis. (PMID:12768229)
• Tyro3 may have roles in signal transduction and cell adhesion (PMID:14623883)
• Axl, Sky and Mer are Gas6 receptors that enhance platelet activation and regulate thrombotic responses (PMID:15733062)
• Results identify and characterise a novel interaction between RanBPM and the related receptor tyrosine kinases, Axl and Sky. (PMID:15964779)
• Here we show the involvement of members of the Tyro3 receptor tyrosine kinase family-Axl, Dtk, and Mer-in cell entry of filoviruses. (PMID:17005688)
• Possible strategies for targeted inhibition of the TAM family in the treatment of human cancer. (PMID:18620092)
• Results identified the receptor protein tyrosine kinase TYRO3 as an upstream regulator of MITF expression by a genome-wide gain-of-function cDNA screen. (PMID:19805117)
• Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor. (PMID:20348395)
• Gas6 and Tyro3, Axl and Mer (TAM) receptors have roles in human and murine platelet activation and thrombus stabilization (PMID:20546121)
• correlation of decreased protein S levels with lupus disease activity is consistent with a role for the TAM receptors in scavenging apoptotic cells and controlling inflammation (PMID:20637106)
• Findings indicate genetic association between MERTK and TYRO3 allelic variants and carotid atherosclerosis. (PMID:20664904)
• Our findings suggest that a TYRO3/AXL-GAS6 autocrine circuit sustains the malignant features of thyroid cancer cells (PMID:21343401)
• expression is downregulated in atherosclerotic carotid plaque (PMID:21384080)
• plasma concentrations of sMer and sTyro3 were significantly increased in patients with active systemic lupus erythematosis and Rheumatoid arthritis (PMID:21496228)
• analysis of novel and selective spiroindoline-based inhibitors of Sky kinase (PMID:22119469)
• Axl,Tyro3,DC-SIGN and LSECtin are identified as new virus receptors for Lassa virus cell entry. (PMID:22156524)
• Gas6, a ligand of Tyro3, exerts an autocrine activities though Tyro3 and Axl in a subgroup of leiomyosarcoma. (PMID:23354874)
• data indicate that Tyro3 may confer increased survival signals in melanoma cells and can be stymied using inhibitory mAbs (PMID:23570341)
• These findings indicate that Tyro3 is a critical signal for synovial hyperplasia, osteoclast differentiation and bone erosion during arthritis. (PMID:23632195)
• [review] Receptor tyrosine kinases Tyro-3, Axl and Mer, collectively designated as TAM, are involved in the clearance of apoptotic cells. (PMID:23662598)
• Low expression of the Syk gene may play an important role in tumorigenesis in esophageal cancer. (PMID:23865365)
• The effects of TYRO3-knockdown by small interfering RNA (siRNA) on proliferation, cell-cycle distribution, and cell signaling in different breast neoplasm cell lines were compared. (PMID:24982338)
• These studies demonstrate that, despite their similarity, TYRO3, AXL, and MER are likely to perform distinct functions in both immunoregulation and the recognition and removal of ACs. (PMID:25074926)
• Tetherin phosphorylation induces the recruitment of Syk which is required for downstream NF-kappaB activation. (PMID:25211072)
• the results of the present study demonstrated that the acquired taxol resistance of ovarian cancer cells was associated with ROS-dependent upregulation in the expression of Tyro3 RTK and the subsequent activation of Akt. (PMID:25815442)
• Significantly increased levels of sMer, sTyro3 and sAxl may be important factors contributing to the deficit in phagocytosis ability in systemic lupus erythematosus . (PMID:25878564)
• The mRNA expression levels of Tyro-3, Axl were decreased in pSS patients. When considering the plasma level, increased levels of soluble Mer was observed with statistically significant difference. (PMID:25881761)
• these data suggest that Tyro3 contributes significantly to tumor growth, aggressiveness and liver dysfunction (PMID:26573872)
• Tyro3 gene dosage modulates Mertk-associated retinal degeneration, provide strong evidence for a direct role for TYRO3 in RPE phagocytosis, and suggest that an eQTL can modify a recessive Inherited photoreceptor degenerations. (PMID:26656104)
• genetic ablation of a receptor tyrosine kinase encoded byTyro3in mice or the functional neutralization of its ortholog in human dendritic cells resulted in enhanced type 2 immunity. (PMID:27034374)
• TYRO3 is overexpressed in the early stage of colon cancer development and aberrant expression of TYRO3 promotes tumorigenesis and induces EMT through the regulation of SNAI1. (PMID:27132510)
• Study identified the Gas6/TAM receptor pathway with Tyro3 and Mer as novel targets in colorectal cancer. (PMID:27486820)
• In this paper, we review the biology of the Gas6/Tyro3, Axl, and MerTK(collectively named TAM system)and the current evidence supporting its potential role in the pathogenesis of multiple sclerosis . (PMID:27801848)
• Phosphatidylserine mediated hyperactivation of TYRO3.TYRO3 promotes epithelial cell efferocytosis in a tyrosine kinase-dependent manner.TYRO3 role in AKT-dependent drug resistance. (PMID:28184013)
• Taken together, our data indicate that elevated plasma Gas6 levels is associated with the severity of disease during HTNV infection in humans, suggesting that Gas6 may play an important role by binding with Tyro3 on monocytes. (PMID:28537534)
• Patients with macroalbuminuria diabetes had higher circulating levels of sMer and more urinary soluble Tyro3 and sMer than normoalbuminuric diabetics. Increased clearance of sTyro3 and sMer was associated with loss of tubular Tyro3 and Mer expression in diabetic nephropathy tissue. During in vitro diabetes, human kidney cells had down-regulation of Tyro3 and Mer mRNA and increased shedding of sTyro3 and sMer. (PMID:28668213)
• These results show that TYRO3, AXL and GAS6 are expressed at higher levels in LMS and expression of its ligands correlates to a worse PFS in LMS patients. (PMID:29024938)
• Serum sTyro3 levels were elevated in rheumatoid arthritis patients and correlated positively with disease activity and bone destruction, which may serve as an important participant in rheumatoid arthritis pathogenesis. (PMID:29148078)
• Data suggest that TYRO3-mediated phosphorylation of ACTN4 is involved in invasiveness of melanoma cells; TYRO3-mediated phosphorylation of ACTN4 requires FAK activation at tyrosine 397. (TYRO3 = TYRO3 protein tyrosine kinase; ACTN4 = actinin alpha 4; FAK = focal adhesion kinase isoform FAK1) (PMID:29274473)
• A meta-analysis of 3 Japanese populations (a total of 2403 Japanese adults) revealed that TYRO3 rs2297377 was associated with atopy and allergic rhinitis (OR = 1.29 and 1.31; P = 0.00041 and 0.0010, respectively). (PMID:30082152)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tyro3	ENSDARG00000005356
mus_musculus	Tyro3	ENSMUSG00000027298
rattus_norvegicus	Tyro3	ENSRNOG00000058586

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), 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), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Tyrosine-protein kinase receptor TYRO3 — Q06418 (reviewed: Q06418)

Alternative names: Tyrosine-protein kinase BYK, Tyrosine-protein kinase DTK, Tyrosine-protein kinase RSE, Tyrosine-protein kinase SKY, Tyrosine-protein kinase TIF

All UniProt accessions (5): Q06418, H0YKZ2, H0YN24, H0YNK6, H3BPR7

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.

Subunit / interactions. Monomer and homodimer. Interacts (via N-terminus) with extracellular ligands TULP1 and GAS6. Interacts with PIK3R1; this interaction increases PI3-kinase activity.

Subcellular location. Cell membrane.

Tissue specificity. Abundant in the brain and lower levels in other tissues.

Post-translational modifications. Autophosphorylated.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.

RefSeq proteins (2): NP_001317193, NP_006284* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF00041, PF07679, PF07714

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 (61 total): strand 16, modified residue 7, glycosylation site 7, sequence variant 7, sequence conflict 5, domain 5, region of interest 2, binding site 2, topological domain 2, disulfide bond 2, signal peptide 1, chain 1, active site 1, transmembrane region 1, mutagenesis site 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1RHF	X-RAY DIFFRACTION	1.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q06418-F1	75.25	0.34

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): 655 (proton acceptor)

Ligand- & substrate-binding residues (2): 524–532; 550

Post-translational modifications (7): 466, 681, 685, 686, 804, 818, 869

Disulfide bonds (2): 64–117, 160–203

Glycosylation sites (7): 63, 191, 230, 240, 293, 366, 380

Mutagenesis-validated functional residues (1):

Position	Phenotype
99	abolishes dimerization.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 307 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, E2F_Q4, MODULE_52, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, MODY_HIPPOCAMPUS_POSTNATAL, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, HNF3ALPHA_Q6, E2F4DP1_01, MORF_BUB1, GOBP_INFLAMMATORY_RESPONSE, CMYB_01, GOBP_PLATELET_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOCC_CELL_SURFACE

GO Biological Process (32): neuron migration (GO:0001764), natural killer cell differentiation (GO:0001779), phagocytosis (GO:0006909), cell adhesion (GO:0007155), signal transduction (GO:0007165), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), neuropeptide signaling pathway (GO:0007218), spermatogenesis (GO:0007283), nervous system development (GO:0007399), cell migration (GO:0016477), forebrain cell migration (GO:0021885), platelet activation (GO:0030168), secretion by cell (GO:0032940), negative regulation of toll-like receptor signaling pathway (GO:0034122), substrate adhesion-dependent cell spreading (GO:0034446), ovulation cycle (GO:0042698), apoptotic cell clearance (GO:0043277), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), negative regulation of neuron apoptotic process (GO:0043524), negative regulation of innate immune response (GO:0045824), negative regulation of inflammatory response (GO:0050728), negative regulation of lymphocyte activation (GO:0051250), neuron apoptotic process (GO:0051402), establishment of localization in cell (GO:0051649), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), vagina development (GO:0060068), neuron cellular homeostasis (GO:0070050), platelet aggregation (GO:0070527), positive regulation of viral life cycle (GO:1903902), protein phosphorylation (GO:0006468), lymphocyte activation (GO:0046649), symbiont entry into host cell (GO:0046718)

GO Molecular Function (11): virus receptor activity (GO:0001618), protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), ATP binding (GO:0005524), phosphatidylinositol 3-kinase binding (GO:0043548), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), nuclear envelope (GO:0005635), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cell surface (GO:0009986), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	2
cellular process	2
cellular anatomical structure	2
generation of neurons	1
lymphocyte differentiation	1
natural killer cell activation	1
endocytosis	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
G protein-coupled receptor signaling pathway	1
developmental process involved in reproduction	1
male gamete generation	1
system development	1
cell motility	1
forebrain development	1
cell activation	1
blood coagulation	1
secretion	1
export from cell	1
toll-like receptor signaling pathway	1
negative regulation of immune system process	1
negative regulation of signal transduction	1
regulation of toll-like receptor signaling pathway	1
cell-substrate adhesion	1
rhythmic process	1
multicellular organismal reproductive process	1
phagocytosis	1
intracellular signaling cassette	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
negative regulation of immune response	1

Protein interactions and networks

STRING

1912 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TYRO3	PROS1	P07225	999
TYRO3	GAS6	Q14393	999
TYRO3	SOCS1	O15524	794
TYRO3	TULP1	O00294	736
TYRO3	IFNAR1	P17181	730
TYRO3	TIMD4	Q96H15	721
TYRO3	CD209	Q9NNX6	719
TYRO3	SOCS3	O14543	718
TYRO3	MFGE8	Q08431	657
TYRO3	GTPBP1	O00178	620
TYRO3	STAT1	P42224	619
TYRO3	CAPN3	P20807	589
TYRO3	STAB2	Q8WWQ8	587
TYRO3	THBS1	P07996	578
TYRO3	ADGRB1	O14514	572

IntAct

197 interactions, top by confidence:

A	B	Type	Score
KRTAP5-9	TYRO3	psi-mi:“MI:0915”(physical association)	0.740
TYRO3	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.740
GRB2	TYRO3	psi-mi:“MI:0915”(physical association)	0.670
KRTAP10-7	TYRO3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	TYRO3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	TYRO3	psi-mi:“MI:0915”(physical association)	0.560
TYRO3	KRT40	psi-mi:“MI:0915”(physical association)	0.560
MDFI	TYRO3	psi-mi:“MI:0915”(physical association)	0.560
TYRO3	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.560
TYRO3	KLK4	psi-mi:“MI:0915”(physical association)	0.560
	TYRO3	psi-mi:“MI:0915”(physical association)	0.560
TYRO3	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
TYRO3	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
KRT40	TYRO3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-2	TYRO3	psi-mi:“MI:0915”(physical association)	0.560
KLK4	TYRO3	psi-mi:“MI:0915”(physical association)	0.560
TYRO3		psi-mi:“MI:0915”(physical association)	0.560

BioGRID (176): TYRO3 (Two-hybrid), TYRO3 (Two-hybrid), TYRO3 (Two-hybrid), KLK4 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), TYRO3 (Affinity Capture-MS), TYRO3 (Affinity Capture-MS), TYRO3 (Two-hybrid), TYRO3 (Two-hybrid), TYRO3 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A6H8M9, A7LCJ3, A8E0Y8, D3YX43, D3YZF7, O14498, O15197, O70394, O70540, P01877, P0C0K6, P0C788, P0DP72, P35590, P40223, P43121, P50895, P70289, Q00657, Q06418, Q06805, Q15109, Q28173, Q5BK54, Q5NVQ6, Q5TJE4, Q61790, Q61826, Q62151, Q62230, Q63495, Q64612, Q6UVK1, Q6UWB1, Q7Z442, Q86VR7, Q8IZF5, Q8R2Y2, Q8VHY0

Diamond homologs: A0JM20, A0M8R7, A0M8S8, A1X150, F1QVU0, G3V9H8, O02466, O35346, P00519, P00520, P00521, P00522, P00529, P06213, P07949, P08069, P08581, P08941, P09760, P0DV84, P10447, P13368, P14617, P16056, P20806, P22182, P23049, P30530, P33497, P34152, P34925, P35546, P35590, P42684, P55144, P55146, P57097, P70451, P97523, P97793

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxo-3-pyridinecarboxamide	down-regulates	TYRO3	“chemical inhibition”
TYRO3	“up-regulates quantity by stabilization”	MLKL	phosphorylation
CBLB	“up-regulates activity”	TYRO3	ubiquitination
TYRO3	“up-regulates activity”	CBLB	phosphorylation
TYRO3	“down-regulates activity”	FOXO3	phosphorylation
GAS6	up-regulates	TYRO3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 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
Ras activation upon Ca2+ influx through NMDA receptor	5	34.8×	2e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	33.2×	2e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	33.2×	2e-05
Assembly and cell surface presentation of NMDA receptors	10	30.9×	1e-10
Dopamine Neurotransmitter Release Cycle	5	30.3×	3e-05
Long-term potentiation	5	29.0×	4e-05
Neurexins and neuroligins	11	26.4×	1e-10
Protein-protein interactions at synapses	7	22.7×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	57.1×	2e-14
protein localization to synapse	6	41.0×	9e-07
receptor clustering	7	39.0×	1e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	31.0×	5e-07
protein-containing complex assembly	10	10.2×	6e-06
cell-cell adhesion	10	9.1×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	2
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3579 predictions. Top by Δscore:

Variant	Effect	Δscore
15:41559380:AGG:A	donor_loss	1.0000
15:41559382:GTAG:G	donor_loss	1.0000
15:41559383:T:G	donor_loss	1.0000
15:41561122:CTCA:C	acceptor_loss	1.0000
15:41561123:TCA:T	acceptor_loss	1.0000
15:41561124:CAG:C	acceptor_loss	1.0000
15:41561125:A:AG	acceptor_gain	1.0000
15:41561125:A:T	acceptor_loss	1.0000
15:41561126:G:GA	acceptor_gain	1.0000
15:41561126:GGT:G	acceptor_gain	1.0000
15:41561126:GGTC:G	acceptor_gain	1.0000
15:41561126:GGTCT:G	acceptor_gain	1.0000
15:41561308:CAGGT:C	donor_loss	1.0000
15:41561311:G:A	donor_loss	1.0000
15:41561312:T:G	donor_loss	1.0000
15:41567531:GGTC:G	donor_gain	1.0000
15:41568208:T:TA	acceptor_gain	1.0000
15:41568215:A:AG	acceptor_gain	1.0000
15:41568216:G:GA	acceptor_gain	1.0000
15:41568360:CAGGT:C	donor_loss	1.0000
15:41568361:AGGT:A	donor_loss	1.0000
15:41568363:G:GG	donor_gain	1.0000
15:41568363:GTAA:G	donor_loss	1.0000
15:41568364:T:A	donor_loss	1.0000
15:41570139:G:GT	donor_gain	1.0000
15:41570140:A:T	donor_gain	1.0000
15:41570236:TTA:T	acceptor_loss	1.0000
15:41570238:A:AG	acceptor_gain	1.0000
15:41570238:AG:A	acceptor_gain	1.0000
15:41570239:G:A	acceptor_loss	1.0000

AlphaMissense

5761 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:41570643:T:C	L508P	1.000
15:41570699:G:A	G527R	1.000
15:41570699:G:C	G527R	1.000
15:41571043:T:A	F529I	1.000
15:41571043:T:C	F529L	1.000
15:41571044:T:G	F529C	1.000
15:41571045:T:A	F529L	1.000
15:41571045:T:G	F529L	1.000
15:41571046:G:C	G530R	1.000
15:41571047:G:A	G530D	1.000
15:41571047:G:T	G530V	1.000
15:41571101:C:A	A548D	1.000
15:41571104:T:A	V549E	1.000
15:41571106:A:G	K550E	1.000
15:41571108:G:C	K550N	1.000
15:41571108:G:T	K550N	1.000
15:41571631:T:C	L566P	1.000
15:41571687:G:T	G585W	1.000
15:41572443:G:A	G585E	1.000
15:41572485:C:A	P599H	1.000
15:41572521:T:C	L611P	1.000
15:41572533:T:C	L615P	1.000
15:41573050:G:C	G642R	1.000
15:41573051:G:A	G642D	1.000
15:41573063:T:C	L646P	1.000
15:41573083:C:G	H653D	1.000
15:41573085:C:A	H653Q	1.000
15:41573085:C:G	H653Q	1.000
15:41573087:G:C	R654P	1.000
15:41573089:G:C	D655H	1.000

dbSNP variants (sampled 300 via entrez): RS1000074476 (15:41579265 C>T), RS1000438821 (15:41563453 G>C), RS1000469918 (15:41563126 G>A), RS1000495139 (15:41560984 A>G,T), RS1000796718 (15:41564657 G>A,C,T), RS1000898515 (15:41580961 C>T), RS1000925637 (15:41574807 C>A), RS1001023520 (15:41557743 T>C), RS1001094158 (15:41580657 GTCTC>G,GTC), RS1001187030 (15:41558526 G>A), RS1001287862 (15:41583737 A>G), RS1001509759 (15:41571657 T>G), RS1001634700 (15:41579335 C>G), RS1001661702 (15:41571144 A>C), RS1001665785 (15:41577665 A>C)

Disease associations

OMIM: gene MIM:600341 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): 46,XX disorder of sex development (MONDO:0017576), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (2): 46,XX difference of sex development (Orphanet:2982), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002463_20	Systemic lupus erythematosus	1.000000e-14
GCST006585_2238	Blood protein levels	2.000000e-09
GCST006585_2651	Blood protein levels	2.000000e-07
GCST008790_47	Urinary albumin-to-creatinine ratio	2.000000e-13
GCST008791_21	Microalbuminuria	4.000000e-09
GCST008794_38	Urinary albumin-to-creatinine ratio	9.000000e-14
GCST009602_21	Metabolic syndrome	2.000000e-10
GCST009640_47	Urinary albumin-to-creatinine ratio	1.000000e-11
GCST010241_63	Apolipoprotein A1 levels	3.000000e-14
GCST010242_406	HDL cholesterol levels	6.000000e-20
GCST90002403_478	Red blood cell count	3.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007778	urinary albumin to creatinine ratio
EFO:0000195	metabolic syndrome
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058489	46, XX Disorders of Sex Development	C12.050.351.875.253.064; C12.200.706.316.064; C12.800.316.064; C16.131.939.316.064; C19.391.119.064
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5314 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

30 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 316,749 (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
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL3622820	ITACITINIB	3	2,274
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL5095079	POVORCITINIB	3	224
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL1738757	REBASTINIB	2	1,478
CHEMBL1976040	ADAVOSERTIB	2	1,738
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL3809489	BEMCENTINIB	2
CHEMBL460702	BMS-777607	2
CHEMBL475251	R-406	2
CHEMBL572878	TOZASERTIB	2
CHEMBL607707	PELITINIB	2
CHEMBL259084	MLN-8054	1
CHEMBL482767	SNS-314	1
CHEMBL49120	PD-0166285	1
CHEMBL574738	AST-487	1
CHEMBL6060997	PF-07265807	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family

Most potent curated ligand interactions (8 total), top 8:

Ligand	Action	Affinity	Parameter
compound 21 [PMID: 23312943]	Inhibition	9.15	pIC50
UNC4203	Inhibition	8.41	pKi
BMS-777607	Inhibition	8.37	pIC50
LDC1267	Inhibition	8.1	pIC50
UNC8969	Inhibition	7.18	pIC50
SLC-391	Inhibition	6.3	pIC50
A-910	Inhibition	6.26	pIC50
MerTK inhibitor 11	Inhibition	6.0	pIC50

Binding affinities (BindingDB)

649 measured of 1112 human assays (1112 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[[5-[5-[(1-adamantylmethylamino)methyl]-2-pyridinyl]-2-(butylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	0.43 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[5-[5-(7-azabicyclo[2.2.1]heptan-7-ylmethyl)-2-pyridinyl]-2-(butylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	0.86 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[5-[5-[(1-adamantylamino)methyl]-2-pyridinyl]-2-(butylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	1 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)amino]methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	1.2 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-methylanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	1.2 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(3-fluoroanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	1.3 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-fluoroanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	1.5 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[2-(butylamino)-5-[4-(4-methylpiperazin-1-yl)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	1.5 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine compounds with anti-mer tyrosine kinase activity
Staurosporine	KD	1.7 nM
4-[5-[4-(azepan-4-ylamino)phenyl]-2-(butylamino)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	2 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine compounds with anti-mer tyrosine kinase activity
4-[2-(4-hydroxybutylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	2.1 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine compounds with anti-mer tyrosine kinase activity
4-[[2-(4-methoxyanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	2.4 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(3-ethynylanilino)-5-pyridin-2-ylpyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	2.6 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[2-(butylamino)-5-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	3 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine compounds with anti-mer tyrosine kinase activity
4-[[2-(2-fluoroanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	3.2 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[2-(4-hydroxybutylamino)-5-[4-(morpholin-4-ylmethyl)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	3.3 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine compounds with anti-mer tyrosine kinase activity
4-[[2-(4-isocyanoanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	3.6 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-ethynylanilino)-5-pyridin-2-ylpyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	3.7 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]-2-[4-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	3.8 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[5-[5-(8-azabicyclo[3.2.1]octan-8-ylmethyl)-2-pyridinyl]-2-(butylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	3.9 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-chloroanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	4.5 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-bromoanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	4.6 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[2-(butylamino)-5-[4-(piperidin-4-ylamino)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	5 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine compounds with anti-mer tyrosine kinase activity
4-[[5-pyridin-2-yl-2-(pyridin-4-ylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	5.1 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-(diethylaminomethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	5.2 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[2-(butylamino)-5-[4-[(1-methylpiperidin-4-yl)amino]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	5.3 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine compounds with anti-mer tyrosine kinase activity
6-[2-(butylamino)-4-[(4-hydroxycyclohexyl)amino]pyrimidin-5-yl]-N-methyl-N-(1-methylpiperidin-4-yl)pyridine-3-carboxamide	IC50	6.5 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-(1-morpholin-4-ylcyclopentyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	7.4 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
N-[4-(4-amino-7-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
methyl 4-[4-amino-5-[4-[(2-oxo-1-phenylpyridine-3-carbonyl)amino]phenyl]pyrrolo[2,1-f][1,2,4]triazin-7-yl]piperidine-1-carboxylate	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-(1-methylsulfonylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methoxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2,5-dioxo-7,8-dihydro-6H-quinoline-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-1-(4-fluorophenyl)-2,5-dioxo-7,8-dihydro-6H-quinoline-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-hydroxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-1-(4-fluorophenyl)-2,5-dioxo-7,8-dihydro-6H-quinoline-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-yl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(2-fluorophenyl)-2,4-dioxo-1-propan-2-yl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(3-fluorophenyl)-2,4-dioxo-1-propan-2-yl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(dimethylcarbamoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-ethyl-3-(3-fluorophenyl)-2,4-dioxo-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-ethyl-3-(3-fluorophenyl)-2,4-dioxo-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(2,5-difluorophenyl)-2,4-dioxo-1-propan-2-yl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(cyclopropanecarbonyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(2-hydroxypropyl)-2,4-dioxo-3-phenyl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(cyclopropanecarbonyl)azetidin-3-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2,4-dioxo-3-phenyl-1-propan-2-yl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-6-methyl-5-(2-methylpyrazol-3-yl)-4-oxo-1-propan-2-ylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-6-(6-methyl-3-pyridinyl)-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-6-methyl-5-(1-methylpyrazol-4-yl)-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-6-methyl-5-morpholin-4-yl-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors

ChEMBL bioactivities

2055 potent at pChembl≥5 of 2273 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL5981096
10.92	IC50	0.012	nM	CHEMBL5782595
10.92	IC50	0.012	nM	CHEMBL5873205
10.92	IC50	0.012	nM	CHEMBL5741930
10.92	IC50	0.012	nM	CHEMBL5817527
10.39	IC50	0.041	nM	CHEMBL5926926
10.39	IC50	0.041	nM	CHEMBL6060115
10.28	IC50	0.052	nM	CHEMBL5981781
10.22	IC50	0.06	nM	CHEMBL5997590
10.01	IC50	0.097	nM	CHEMBL5745182
10.00	IC50	0.1	nM	CHEMBL5908100
9.89	IC50	0.13	nM	CHEMBL5767211
9.89	IC50	0.13	nM	CHEMBL5993962
9.89	IC50	0.13	nM	CHEMBL5874363
9.85	IC50	0.14	nM	CHEMBL6022455
9.85	IC50	0.14	nM	CHEMBL5916277
9.80	IC50	0.16	nM	CHEMBL6053094
9.80	IC50	0.16	nM	CHEMBL6019126
9.80	IC50	0.16	nM	CHEMBL5986184
9.77	IC50	0.17	nM	CHEMBL5824153
9.77	IC50	0.17	nM	CHEMBL5883347
9.77	IC50	0.17	nM	CHEMBL5934278
9.72	IC50	0.19	nM	CHEMBL5846250
9.70	IC50	0.2	nM	CHEMBL5967645
9.64	IC50	0.23	nM	CHEMBL5803120
9.57	IC50	0.27	nM	CHEMBL6052995
9.57	IC50	0.27	nM	CHEMBL5822883
9.55	IC50	0.28	nM	CHEMBL5919842
9.52	IC50	0.3	nM	CHEMBL6065829
9.49	IC50	0.32	nM	CHEMBL5934837
9.47	IC50	0.34	nM	CHEMBL5913672
9.47	IC50	0.34	nM	CHEMBL5745525
9.43	IC50	0.37	nM	CHEMBL5908464
9.38	IC50	0.42	nM	CHEMBL5825584
9.32	IC50	0.48	nM	CHEMBL5741898
9.24	IC50	0.58	nM	CHEMBL5825621
9.22	IC50	0.6	nM	CHEMBL5873205
9.15	IC50	0.7	nM	CHEMBL2312654
9.05	IC50	0.9	nM	CHEMBL5814386
9.00	IC50	1	nM	CHEMBL4873571
9.00	IC50	1	nM	CHEMBL6010989
8.92	IC50	1.2	nM	CHEMBL5639725
8.92	IC50	1.2	nM	CHEMBL6005928
8.92	IC50	1.2	nM	CHEMBL4279154
8.89	IC50	1.3	nM	CHEMBL5895995
8.85	IC50	1.4	nM	CHEMBL6053185
8.84	IC50	1.45	nM	STAUROSPORINE
8.83	EC50	1.47	nM	CHEMBL6192562
8.80	IC50	1.6	nM	CHEMBL5839005
8.80	IC50	1.6	nM	CHEMBL5871911

PubChem BioAssay actives

432 with measured affinity, of 2147 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
2-N-(3,5-dichlorophenyl)-4-N-[4-(dimethylamino)cyclohexyl]-5-(3-methyl-1,2-oxazol-5-yl)pyrimidine-2,4-diamine	721419: Inhibition of Sky (unknown origin) by ELISA kinase assay in presence of 60 uM ATP	ic50	0.0007	uM
N-[4-[[2-(cyclopropanecarbonylamino)-4-pyridinyl]oxy]-3-fluorophenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1764508: Inhibition of recombinant human RSE (451 to end residues) using KVEKIGEGTYGVVYK as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay	ic50	0.0010	uM
3-[[5-(4-fluorophenyl)-2H-pyrazolo[3,4-b]pyridin-3-yl]carbamoyl]benzoic acid	2144598: Inhibition of SKY (unknown origin)	ic50	0.0012	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	1715131: Inhibition of human TYRO3 using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0014	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	625057: Binding constant for TYRO3 kinase domain	kd	0.0020	uM
2-(3,5-dichloroanilino)-4-[[4-(dimethylamino)cyclohexyl]amino]-N-(1-methylpiperidin-4-yl)pyrimidine-5-carboxamide	721419: Inhibition of Sky (unknown origin) by ELISA kinase assay in presence of 60 uM ATP	ic50	0.0020	uM
1-[(4-aminocyclohexyl)methyl]-N-butyl-3-(4-piperazin-1-ylphenyl)pyrazolo[3,4-d]pyrimidin-6-amine	663572: Inhibition of Tyro3 using EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluid capillary electrophoresis assay	ic50	0.0029	uM
2-(3,5-dichloroanilino)-4-[[(2S)-1-hydroxybutan-2-yl]amino]-N-(1-methylpiperidin-4-yl)pyrimidine-5-carboxamide	721419: Inhibition of Sky (unknown origin) by ELISA kinase assay in presence of 60 uM ATP	ic50	0.0030	uM
4-[5-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409258: Inhibition of N-terminal GST-tagged human TYRO3 cytoplasmic domain (453 to 890 end residues) expressed in baculovirus expression system using fluorecence-labeled substrate by MCE assay	ic50	0.0031	uM
N-(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)-1H-indazole-3-carboxamide	2144598: Inhibition of SKY (unknown origin)	ic50	0.0032	uM
4-[5-[4-(7-azabicyclo[2.2.1]heptan-7-ylmethyl)phenyl]-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0034	uM
4-[2-[[(2S)-hexan-2-yl]amino]-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0043	uM
N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-1-(4-fluorophenyl)-4-methoxy-2-oxopyridine-3-carboxamide	1691582: Inhibition of Tyro3 (unknown origin)	ic50	0.0043	uM
N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	2151500: Inhibition of Tyro-3 (unknown origin) by kinase profiling assay	ic50	0.0043	uM
4-[5-[4-[[2-(diethylamino)ethylamino]methyl]phenyl]-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0044	uM
4-[2-(butylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409258: Inhibition of N-terminal GST-tagged human TYRO3 cytoplasmic domain (453 to 890 end residues) expressed in baculovirus expression system using fluorecence-labeled substrate by MCE assay	ic50	0.0058	uM
1-[(4-aminocyclohexyl)methyl]-N-(3-phenylpropyl)-3-(4-piperazin-1-ylphenyl)pyrazolo[3,4-d]pyrimidin-6-amine	663572: Inhibition of Tyro3 using EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluid capillary electrophoresis assay	ic50	0.0059	uM
2-(3,5-dichloroanilino)-N-(1-methylpiperidin-4-yl)-4-[[(3S)-2-oxoazepan-3-yl]amino]pyrimidine-5-carboxamide	721419: Inhibition of Sky (unknown origin) by ELISA kinase assay in presence of 60 uM ATP	ic50	0.0060	uM
4-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-2-(pentan-2-ylamino)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0067	uM
4-[2-(2-ethylbutylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0067	uM
4-[2-[[(2S)-heptan-2-yl]amino]-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0069	uM
(6S)-6-amino-22-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1,8,17,19,25-pentazatricyclo[16.5.2.021,24]pentacosa-18,20,22,24-tetraen-7-one	1325799: Inhibition of Tyro3 (unknown origin) by microfluidic capillary electrophoresis assay	ic50	0.0075	uM
N-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-4-ethoxy-1-(4-fluoro-2-methylphenyl)pyrazole-3-carboxamide	2146586: Displacement of kinase tracer 236 from GST-tagged Tyro3 (unknown origin) assessed as inhibition constant incubated for 1 hr by HTRF based TR-FRET assay	ic50	0.0080	uM
4-[2-[[(2S)-pentan-2-yl]amino]-5-(2-piperazin-1-yl-4-pyridinyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0090	uM
2-(3,5-dichloroanilino)-N-(1-methylpiperidin-4-yl)-4-(oxan-4-ylamino)pyrimidine-5-carboxamide	721419: Inhibition of Sky (unknown origin) by ELISA kinase assay in presence of 60 uM ATP	ic50	0.0090	uM
4-[5-[4-(morpholin-4-ylmethyl)phenyl]-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0100	uM
1-(4-fluorophenyl)-N-[3-fluoro-4-[(3-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]phenyl]-2,3-dimethyl-5-oxopyrazole-4-carboxamide	1733271: Inhibition of GST-tagged Tyro3 (unknown origin) (453 to 890 residues) using Axltide (KKSRGDYMTMQIG-acid) peptide as substrate preincubated for 30 mins followed by substrate and ATP addition at Km concentration measured after 180 mins by RapidFire LC-MS analysis	ic50	0.0100	uM
2-(3,5-dichloroanilino)-4-[[(3R,4S)-4-hydroxyoxolan-3-yl]amino]-N-(1-methylpiperidin-4-yl)pyrimidine-5-carboxamide	721419: Inhibition of Sky (unknown origin) by ELISA kinase assay in presence of 60 uM ATP	ic50	0.0100	uM
4-[5-[4-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]phenyl]-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0110	uM
4-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0120	uM
4-[2-(2-methylbutylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0120	uM
4-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-2-[[(2R)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0130	uM
(6S)-6-amino-20-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1,8,15,17,23-pentazatricyclo[14.5.2.019,22]tricosa-16,18,20,22-tetraen-7-one	1325799: Inhibition of Tyro3 (unknown origin) by microfluidic capillary electrophoresis assay	ic50	0.0130	uM
1-[(4-aminocyclohexyl)methyl]-N-butyl-3-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[3,4-d]pyrimidin-6-amine	663572: Inhibition of Tyro3 using EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluid capillary electrophoresis assay	ic50	0.0140	uM
(2,6-dimethyl-4-pyridinyl)-[4-[7-(4-hydroxycyclohexyl)-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]methanone	1779135: Inhibition of N-terminal GST-tagged TYRO3 (453 to 890 residues) (unknown origin) cytoplasmic domain expressed in Sf21 cells	ic50	0.0150	uM
(3S,4R)-4-[[5-bromo-2-(3,5-dichloroanilino)pyrimidin-4-yl]amino]oxolan-3-ol	721419: Inhibition of Sky (unknown origin) by ELISA kinase assay in presence of 60 uM ATP	ic50	0.0150	uM
1-(3,4-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-5-yl)-3-N-[(7S)-7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]-1,2,4-triazole-3,5-diamine	1374814: Inhibition of wild-type human partial length TYRO3 (S497 to T814 residues) expressed in bacterial expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP	ic50	0.0170	uM
4-[2-(2-cyclopropylethylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1185902: Inhibition of Tyro3 (unknown origin) by Off-chip Mobility Shift Assay	ic50	0.0170	uM
[4-[7-(4-hydroxycyclohexyl)-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]-[(3S)-1-methylpiperidin-3-yl]methanone	1779117: Inhibition of TYRO3 (unknown origin)	ic50	0.0180	uM
1-[(4-aminocyclohexyl)methyl]-3-phenyl-N-(2-phenylethyl)pyrazolo[3,4-d]pyrimidin-6-amine	663572: Inhibition of Tyro3 using EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluid capillary electrophoresis assay	ic50	0.0180	uM
Crizotinib	2161842: Inhibition of human N-terminal GST-fused TYRO3 cytoplasmic domain (453 to 890(end) residues) expressed in baculovirus expression system using CSKtide as substrate measured after 1 hr by off-chip mobility shift assay relative to control	ic50	0.0200	uM
3-amino-6-[3-(1-ethylpyrazol-4-yl)phenyl]-N-(5-hydroxy-2-adamantyl)pyrazine-2-carboxamide	656547: Inhibition of human recombinant Sky using poly-GT as substrate and [33P]ATP after 40 mins by beta counting	ic50	0.0200	uM
3-amino-N-(5-hydroxy-2-adamantyl)-6-[3-(1-methylpyrazol-4-yl)phenyl]pyrazine-2-carboxamide	656547: Inhibition of human recombinant Sky using poly-GT as substrate and [33P]ATP after 40 mins by beta counting	ic50	0.0200	uM
4-[5-[3-(4-methylpiperazin-1-yl)phenyl]-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0210	uM
4-[[2-(butylamino)-5-[5-[(dimethylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	1058164: Inhibition of Tyro-3 kinase (unknown origin) using 5-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluidic capillary electrophoresis assay	ic50	0.0210	uM
4-[[2-(butylamino)-5-[5-[(2-hydroxyethylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	1058164: Inhibition of Tyro-3 kinase (unknown origin) using 5-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluidic capillary electrophoresis assay	ic50	0.0210	uM
4-[2-(butylamino)-5-[4-(4-methylpiperazin-1-yl)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0220	uM
20-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1,15,17,23-tetrazatricyclo[14.5.2.019,22]tricosa-16,18,20,22-tetraen-6-ol	1325799: Inhibition of Tyro3 (unknown origin) by microfluidic capillary electrophoresis assay	ic50	0.0220	uM
1-[(4-aminocyclohexyl)methyl]-N-(3-phenylpropyl)-3-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[3,4-d]pyrimidin-6-amine	663572: Inhibition of Tyro3 using EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluid capillary electrophoresis assay	ic50	0.0220	uM
4-[2-[[(2S)-pentan-2-yl]amino]-5-(1-piperidin-4-ylpyrazol-4-yl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409233: Inhibition of TYRO3 (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0240	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	affects expression, decreases expression	4
trichostatin A	affects cotreatment, decreases expression, affects expression, decreases reaction	3
sodium arsenite	affects methylation, increases expression	3
Tretinoin	decreases expression	3
Vorinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Cisplatin	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
methyleugenol	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects response to substance, affects expression	1
aflatoxin B2	decreases methylation	1
cupric chloride	increases expression	1
epigallocatechin gallate	decreases expression	1
tamibarotene	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Adenosine Diphosphate	increases response to substance	1
Atrazine	increases expression	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Dexamethasone	decreases expression	1
Doxorubicin	affects expression	1

ChEMBL screening assays

380 unique, capped per target: 376 binding, 3 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1024898	Binding	Binding affinity to human TYRO3 at 10 uM relative to control	Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. — J Med Chem
CHEMBL1963714	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: TYRO3	PubChem BioAssay data set
CHEMBL6121367	Toxicity	Inhibition of N-terminal GST-tagged recombinant human TYRO3 (455 to end residues) expressed in baculovirus-infected Sf9 cells using biotin-labeled TK and ATP as substrate preincubated with enzyme for 30 mins followed by substrate addition a	Discovery of A-910, a Highly Potent and Orally Bioavailable Dual MerTK/Axl-Selective Tyrosine Kinase Inhibitor. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9V8	Ubigene HEK293 TYRO3 KO	Transformed cell line	Female
CVCL_TV35	HAP1 TYRO3 (-) 1	Cancer cell line	Male
CVCL_TV36	HAP1 TYRO3 (-) 2	Cancer cell line	Male
CVCL_TV37	HAP1 TYRO3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome