LMTK3

Summary

LMTK3 (lemur tyrosine kinase 3, HGNC:19295) is a protein-coding gene on chromosome 19q13.33, encoding Serine/threonine-protein kinase LMTK3 (Q96Q04). Protein kinase which phosphorylates ESR1 (in vitro) and protects it against proteasomal degradation.

Predicted to enable protein kinase activity. Predicted to be involved in chromatin remodeling. Predicted to be located in Golgi membrane; axon; and dendrite.

Source: NCBI Gene 114783 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 226 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001388485

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19295
Approved symbol	LMTK3
Name	lemur tyrosine kinase 3
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1883, LMR3, AATYK3, TYKLM3, PPP1R101
Ensembl gene	ENSG00000142235
Ensembl biotype	protein_coding
OMIM	619624
Entrez	114783

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000598924, ENST00000600059, ENST00000647709, ENST00000648216, ENST00000650440, ENST00000672160, ENST00000673139

RefSeq mRNA: 2 — MANE Select: NM_001388485 NM_001080434, NM_001388485

CCDS: CCDS46136

Canonical transcript exons

ENST00000600059 — 15 exons

Exon	Start	End
ENSE00000953087	48502909	48502996
ENSE00000953088	48502433	48502581
ENSE00000953089	48501478	48501562
ENSE00000953090	48501283	48501404
ENSE00000953091	48500996	48501145
ENSE00001058763	48491404	48491539
ENSE00001058764	48508851	48508969
ENSE00001058768	48510023	48510173
ENSE00001116372	48510459	48510592
ENSE00001116373	48497393	48499917
ENSE00001116374	48493694	48494109
ENSE00001116375	48509437	48509513
ENSE00001131060	48491108	48491245
ENSE00001245524	48485271	48485789
ENSE00003916061	48511501	48511835

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 93.26.

FANTOM5 (CAGE): breadth broad, TPM avg 10.7797 / max 875.5705, expressed in 818 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181860	6.5462	419
181865	1.2277	100
181857	0.8346	369
181863	0.7074	71
181855	0.4293	197
181856	0.3201	179
181858	0.2415	136
181867	0.2068	105
181866	0.1136	53
181864	0.0691	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	93.26	gold quality
cortical plate	UBERON:0005343	92.88	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.38	gold quality
anterior cingulate cortex	UBERON:0009835	92.05	gold quality
nucleus accumbens	UBERON:0001882	91.99	gold quality
putamen	UBERON:0001874	91.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.06	gold quality
caudate nucleus	UBERON:0001873	90.68	gold quality
cerebellar hemisphere	UBERON:0002245	90.21	gold quality
cerebellar cortex	UBERON:0002129	90.11	gold quality
prefrontal cortex	UBERON:0000451	89.87	gold quality
amygdala	UBERON:0001876	89.47	gold quality
cerebellum	UBERON:0002037	88.59	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.34	gold quality
neocortex	UBERON:0001950	88.12	gold quality
frontal cortex	UBERON:0001870	88.06	gold quality
hypothalamus	UBERON:0001898	88.05	gold quality
forebrain	UBERON:0001890	86.06	gold quality
adenohypophysis	UBERON:0002196	85.79	gold quality
cerebral cortex	UBERON:0000956	85.71	gold quality
brain	UBERON:0000955	85.61	gold quality
pituitary gland	UBERON:0000007	84.96	gold quality
Ammon’s horn	UBERON:0001954	84.05	gold quality
lower esophagus mucosa	UBERON:0035834	81.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.20	gold quality
temporal lobe	UBERON:0001871	81.08	gold quality
ganglionic eminence	UBERON:0004023	80.60	gold quality
substantia nigra	UBERON:0002038	80.10	gold quality
superior frontal gyrus	UBERON:0002661	79.11	gold quality
spinal cord	UBERON:0002240	78.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.41

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 21)

• abundance and intronic polymorphism associated with breast cancer survival and response to endocrine therapies (PMID:21602804)
• Higher LMTK3 expression is associated with more aggressive breast cancers. (PMID:21671015)
• role for LMTK3 in both innate (intrinsic) and acquired (adaptive) endocrine resistance in breast cancer (PMID:22869149)
• harboring rs8108419 G/G genotype of the LMTK3 was associated with OS in the Japanese females (HR, 3.04; 95% CI, 1.08-8.56; P = 0.035) and the U.S. males (HR, 3.39; 95% CI, 1.31-8.80; P = 0.012). (PMID:23918832)
• miR-34a inhibits breast cancer proliferation by targeting LMTK3 (PMID:24050776)
• Kaplan-Meier survival curves showed that colorectal cancer patients with high levels of sLMTK3 had a poorer overall survival rate when compared with those of patients with low levels of sLMTK3. (PMID:24174317)
• These computational reports provide more information on the structure-function relationship of LMTK3 with ATP. (PMID:24619340)
• LMTK3 expression was an independent prognostic factor for colorectal cancer patients (PMID:24695631)
• abundance of LMTK3 positively correlated with that of the integrin beta1 subunit in breast cancer patient’s tumors (PMID:24939894)
• Results show that high expression of LMTK3 is an independent prognostic factor in estrogen receptor alpha-positive breast cancer patients receiving adjuvant endocrine therapy (PMID:25163465)
• The serum LMTK3 level was significantly increased in human non-small cell lung cancer, and could be used as a potential and valuable biomarker (PMID:25755755)
• LMTK3 functions at distal regions in tethering the chromatin to the nuclear periphery, resulting in H3K9me3 modification and gene silencing. (PMID:26212333)
• LMTK3 escapes tumour suppressor miRNAs via sequestration of DDX5. (PMID:26739063)
• The serum LMTK3 level was significantly increased in 102 thyroid carcinoma patients compared with 52 benign thyroid tumor patients and 50 healthy volunteers (P=0.001). The protein and mRNA expression of LMTK3 was markedly higher in thyroid cancer patients compared with patients with benign thyroid tumors. LMTK3 knockdown retarded proliferation, invasion and migration in SW579 cells. (PMID:28260052)
• Phosphorylation of RCP at Ser(435) by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser(897) by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart. (PMID:28294115)
• LMTK-3 increased phosphorylated p38 and JNK, but decreased phosphorylated ERK1/2 and AKT. Overexpression of LMTKs may contribute to biologic behavior changes of PCa, especially cell apoptosis. (PMID:28848113)
• LMTK3 expression and its role in the drug resistance in breast cancer. (PMID:29540829)
• targeting of LMTK3 with siRNA delayed KIT-dependent GIST growth in a xenograft model. Our data suggest the potential of LMTK3 as a target for treatment of patients with KIT-mutant cancer, particularly after failure of KIT TKIs. (PMID:30242244)
• Our findings support a model in which the MIR2052HG regulates LMTK3 via EGR1, and LMTK3 regulates ERalpha stability via the PKC/MEK/ERK/RSK1 axis. These results reveal a direct role of MIR2052HG in LMTK3 regulation and raise the possibilities of targeting MIR2052HG or LMTK3 in ERalpha-positive breast cancer. (PMID:30944027)
• LMTK3 promotes tumorigenesis in bladder cancer via the ERK/MAPK pathway. (PMID:32865871)
• Lemur tyrosine kinase-3 (LMTK3) induces chemoresistance to cetuximab in colorectal cancer via the ERK/MAPK pathway. (PMID:34516351)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lmtk3	ENSDARG00000029114
mus_musculus	Lmtk3	ENSMUSG00000062044
rattus_norvegicus	Lmtk3	ENSRNOG00000021048

Paralogs (1): AATK (ENSG00000181409)

Protein

Protein identifiers

Serine/threonine-protein kinase LMTK3 — Q96Q04 (reviewed: Q96Q04)

Alternative names: Lemur tyrosine kinase 3

All UniProt accessions (6): Q96Q04, A0A3B3IRV9, A0A3B3ISL5, A0A3B3ITQ7, A0A5F9ZH67, A0A5F9ZHT0

UniProt curated annotations — full annotation on UniProt →

Function. Protein kinase which phosphorylates ESR1 (in vitro) and protects it against proteasomal degradation. May also regulate ESR1 levels indirectly via a PKC-AKT-FOXO3 pathway where it decreases the activity of PKC and the phosphorylation of AKT, thereby increasing binding of transcriptional activator FOXO3 to the ESR1 promoter and increasing ESR1 transcription. Involved in endocytic trafficking of N-methyl-D-aspartate receptors (NMDAR) in neurons.

Subunit / interactions. Interacts with ESR1. Interacts with AP-2 complex subunit alpha.

Subcellular location. Membrane. Cell projection. Axon. Dendrite. Golgi apparatus membrane.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family.

RefSeq proteins (2): NP_001073903, NP_001375414* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site

Pfam: PF07714

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (67 total): compositionally biased region 17, helix 13, strand 9, region of interest 8, modified residue 5, binding site 2, glycosylation site 2, sequence variant 2, sequence conflict 2, turn 2, signal peptide 1, chain 1, transmembrane region 1, active site 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6SEQ	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96Q04-F1	47.17	0.15

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): 266 (proton acceptor)

Ligand- & substrate-binding residues (2): 139–147; 164

Post-translational modifications (5): 232, 490, 531, 535, 981

Glycosylation sites (2): 1081, 1405

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): MODULE_255, MODULE_317, DING_LUNG_CANCER_BY_MUTATION_RATE, GOCC_NEURON_PROJECTION, MODULE_342, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, MODULE_69, GOCC_SOMATODENDRITIC_COMPARTMENT, GOCC_AXON, GOMF_PROTEIN_KINASE_ACTIVITY, MODULE_154, GOMF_KINASE_ACTIVITY, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_UP, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING

GO Biological Process (1): protein phosphorylation (GO:0006468)

GO Molecular Function (10): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): Golgi membrane (GO:0000139), axon (GO:0030424), dendrite (GO:0030425), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein kinase activity	3
neuron projection	2
phosphorylation	1
protein modification process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
dendritic tree	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LMTK3	PPP1CA	P08129	469
LMTK3	ESR1	P03372	410
LMTK3	CUEDC2	Q9H467	347
LMTK3	AKIRIN1	Q9H9L7	344
LMTK3	RAB11FIP1	Q6WKZ4	323
LMTK3	WDR97	A6NE52	317
LMTK3	FOXN2	P32314	310
LMTK3	GRB2	P29354	293
LMTK3	LRRC24	Q50LG9	279
LMTK3	ZNF707	Q96C28	278
LMTK3	FOXO3	O43524	277
LMTK3	LRRC14	Q15048	275
LMTK3	TXNDC12	O95881	273
LMTK3	ITGB1	P05556	272
LMTK3	GLI4	P10075	267
LMTK3	PLEKHF2	Q9H8W4	267

IntAct

11 interactions, top by confidence:

A	B	Type	Score
LMTK3	ESR1	psi-mi:“MI:0915”(physical association)	0.540
LMTK3	ESR1	psi-mi:“MI:0217”(phosphorylation reaction)	0.540
EPS15	LMTK3	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1CA	LMTK3	psi-mi:“MI:0407”(direct interaction)	0.440
LMTK3	GPI	psi-mi:“MI:0914”(association)	0.420
LTK	PIK3R2	psi-mi:“MI:0914”(association)	0.420
CUL4B	GGTLC3	psi-mi:“MI:0914”(association)	0.350
LMTK3	C11orf98	psi-mi:“MI:2364”(proximity)	0.270
LMTK3	ZBTB16	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (112): LMTK3 (Synthetic Growth Defect), LMTK3 (Synthetic Lethality), LMTK3 (Affinity Capture-MS), LMTK3 (Affinity Capture-MS), ZBTB16 (Two-hybrid), LMTK3 (Affinity Capture-RNA), LMTK3 (Affinity Capture-MS), HSPA1B (Proximity Label-MS), ITSN2 (Proximity Label-MS), SMARCA5 (Proximity Label-MS), NEDD1 (Proximity Label-MS), KARS (Proximity Label-MS), GNB2L1 (Proximity Label-MS), CALR (Proximity Label-MS), RAB11FIP5 (Proximity Label-MS)

ESM2 similar proteins: A0A1B0GUA5, A0A286YF58, A0A494C0N9, A0A494C0Y3, A0A7I2V3R4, A0JNN8, A2ARS0, A2VDX9, A5PJP1, A6NGB7, A8MVW0, C9JTQ0, O14511, O14559, O35392, O35569, O43541, O60548, O70220, P0DPE3, Q08102, Q14V87, Q19A40, Q29RK8, Q2HJ59, Q3TYP4, Q5BLP8, Q5T442, Q63244, Q6F5E0, Q6QNY0, Q6VUP9, Q80WY3, Q80XF7, Q8BQU6, Q8K025, Q8K071, Q8TD94, Q8WY41, Q8WZ71

Diamond homologs: A0JNB0, A1Y2K1, F8W3R9, O02466, O13147, O42422, O45539, O73798, O73878, O76997, P00523, P00529, P00530, P00541, P04629, P06213, P08069, P08922, P08941, P09208, P09759, P09769, P12931, P13368, P14085, P14616, P14617, P15054, P15127, P15208, P15209, P24062, P24604, P27446, P28693, P33497, P35739, P39688, P41239, P42159

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	198
Likely benign	9
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2481 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48485796:A:AC	acceptor_gain	1.0000
19:48485801:C:CT	acceptor_gain	1.0000
19:48491397:T:TA	donor_gain	1.0000
19:48491398:CCTCA:C	donor_loss	1.0000
19:48491399:CTCAC:C	donor_loss	1.0000
19:48491400:TCA:T	donor_loss	1.0000
19:48491401:CACC:C	donor_loss	1.0000
19:48491402:A:AC	donor_gain	1.0000
19:48491403:C:A	donor_loss	1.0000
19:48491403:C:CC	donor_gain	1.0000
19:48491539:CCTG:C	acceptor_gain	1.0000
19:48491549:CAGAT:C	acceptor_gain	1.0000
19:48493688:CCGCA:C	donor_loss	1.0000
19:48493689:CGCAC:C	donor_loss	1.0000
19:48493690:GCACC:G	donor_loss	1.0000
19:48493691:CACCT:C	donor_loss	1.0000
19:48493692:ACCTG:A	donor_loss	1.0000
19:48500990:CCTCA:C	donor_loss	1.0000
19:48500991:CTCA:C	donor_loss	1.0000
19:48500992:TCAC:T	donor_loss	1.0000
19:48500993:CACCA:C	donor_loss	1.0000
19:48500994:A:AC	donor_gain	1.0000
19:48500995:C:CC	donor_gain	1.0000
19:48500995:C:CT	donor_loss	1.0000
19:48501141:GGGAC:G	acceptor_gain	1.0000
19:48501142:GGAC:G	acceptor_gain	1.0000
19:48501143:GAC:G	acceptor_gain	1.0000
19:48501144:AC:A	acceptor_gain	1.0000
19:48501145:CC:C	acceptor_gain	1.0000
19:48501146:C:CC	acceptor_gain	1.0000

AlphaMissense

9265 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48493710:A:T	V1359D	1.000
19:48499450:A:T	I540N	1.000
19:48499626:C:A	W481C	1.000
19:48499626:C:G	W481C	1.000
19:48499666:A:T	V468D	1.000
19:48499672:A:G	L466P	1.000
19:48499895:A:G	W392R	1.000
19:48499895:A:T	W392R	1.000
19:48501119:A:G	L343P	1.000
19:48501126:A:G	W341R	1.000
19:48501126:A:T	W341R	1.000
19:48501138:C:A	G337W	1.000
19:48501138:C:G	G337R	1.000
19:48501138:C:T	G337R	1.000
19:48501284:A:G	W334R	1.000
19:48501284:A:T	W334R	1.000
19:48501357:C:A	W309C	1.000
19:48501357:C:G	W309C	1.000
19:48501359:A:G	W309R	1.000
19:48501359:A:T	W309R	1.000
19:48502457:A:G	L257P	1.000
19:48502470:C:A	G253W	1.000
19:48502470:C:G	G253R	1.000
19:48502470:C:T	G253R	1.000
19:48502931:A:G	L208P	1.000
19:48502934:A:G	L207P	1.000
19:48508875:A:G	F178S	1.000
19:48508911:A:G	L166P	1.000
19:48493700:G:C	F1362L	0.999
19:48493700:G:T	F1362L	0.999

dbSNP variants (sampled 300 via entrez): RS1000036197 (19:48514091 G>A,C), RS1000102552 (19:48502385 T>A,G), RS1000107611 (19:48515673 T>C), RS1000257394 (19:48496217 C>G,T), RS1000305799 (19:48501632 C>T), RS1000408801 (19:48514514 T>C), RS1000482033 (19:48490376 A>C), RS1000535724 (19:48495082 G>A,T), RS1000586787 (19:48494940 G>T), RS1000763782 (19:48489446 G>A,T), RS1000829909 (19:48507601 T>C), RS1000848757 (19:48488843 G>A), RS1000905159 (19:48507262 G>A), RS1001028596 (19:48501067 G>A,C), RS1001215945 (19:48515634 C>T)

Disease associations

OMIM: gene MIM:619624 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009650_11	Serum carcinoembryonic antigen levels	7.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005760	serum carcinoembryonic antigen measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523432 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,916 (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
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL575448	BMS-754807	2	406

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type XVIII RTKs: LMR family

ChEMBL bioactivities

11 potent at pChembl≥5 of 11 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.93	IC50	0.1175	nM	CHEMBL4450227
9.88	IC50	0.1318	nM	GF-109203
7.10	IC50	79.43	nM	K-252A
6.68	IC50	210	nM	CHEMBL4637017
6.65	IC50	226	nM	CHEMBL4647760
6.51	IC50	308	nM	CHEMBL4635320
6.50	IC50	318	nM	CHEMBL4649625
6.18	IC50	654	nM	CHEMBL4638119
5.79	IC50	1609	nM	CHEMBL4649046
5.50	IC50	3161	nM	BMS-754807
5.33	IC50	4653	nM	ENTRECTINIB

PubChem BioAssay actives

9 with measured affinity, of 14 total; 9 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
(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	1659479: Inhibition of LMTK3 (unknown origin)	ic50	<0.0001	uM
N-[(2S)-1-[(5S)-2-amino-5-(2-methylpropyl)-4,5-dihydroimidazol-1-yl]-3-(4-hydroxyphenyl)propan-2-yl]-2-chlorobenzenesulfonamide	1659479: Inhibition of LMTK3 (unknown origin)	ic50	0.2100	uM
N-[(2S)-1-[(5S)-2-amino-5-(cyclohexylmethyl)-4,5-dihydroimidazol-1-yl]-3-(4-hydroxyphenyl)propan-2-yl]-2-chlorobenzenesulfonamide	1659479: Inhibition of LMTK3 (unknown origin)	ic50	0.2260	uM
N-[(2S)-1-[(5S)-2-amino-5-(2-methylpropyl)-4,5-dihydroimidazol-1-yl]-3-(4-hydroxyphenyl)propan-2-yl]-4-methylbenzenesulfonamide	1659479: Inhibition of LMTK3 (unknown origin)	ic50	0.3080	uM
N-[(2S)-1-[(5S)-2-amino-5-(cyclohexylmethyl)-4,5-dihydroimidazol-1-yl]-3-(4-hydroxyphenyl)propan-2-yl]-4-methylbenzenesulfonamide	1659479: Inhibition of LMTK3 (unknown origin)	ic50	0.3180	uM
N-[(2S)-1-[(5S)-2-amino-5-(2-methylpropyl)-4,5-dihydroimidazol-1-yl]-3-phenylpropan-2-yl]benzenesulfonamide	1659479: Inhibition of LMTK3 (unknown origin)	ic50	0.6540	uM
N-[(2S)-1-[(5S)-2-amino-5-(cyclohexylmethyl)-4,5-dihydroimidazol-1-yl]-3-phenylpropan-2-yl]benzenesulfonamide	1659479: Inhibition of LMTK3 (unknown origin)	ic50	1.6090	uM
(2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-2-methylpyrrolidine-2-carboxamide	1659479: Inhibition of LMTK3 (unknown origin)	ic50	3.1610	uM
Entrectinib	1659479: Inhibition of LMTK3 (unknown origin)	ic50	4.6530	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cadmium Chloride	increases expression	2
propionaldehyde	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	affects expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression, affects cotreatment	1
Lead	increases expression	1
Mustard Gas	increases expression	1
Niclosamide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	decreases methylation	1
Sodium Selenite	decreases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4418914	Binding	Inhibition of N-terminal GST tag LMTK3 kinase domain (133 to 415 amino acids) (unknown origin) expressed in insect cells incubated for 120 mins by radiometric fluorescent detection based CisBio KinEASE STK-S1 kit based assay	Methods for categorising cancer such as breast cancer

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SV73	HAP1 LMTK3 (-) 1	Cancer cell line	Male
CVCL_SV74	HAP1 LMTK3 (-) 2	Cancer cell line	Male
CVCL_SV75	HAP1 LMTK3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder