SRMS

Summary

SRMS (src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites, HGNC:11298) is a protein-coding gene on chromosome 20q13.33, encoding Tyrosine-protein kinase Srms (Q9H3Y6). Non-receptor tyrosine-protein kinase which phosphorylates DOK1 on tyrosine residues.

Enables protein tyrosine kinase activity. Involved in peptidyl-tyrosine autophosphorylation and positive regulation of TORC1 signaling. Located in cytoplasm.

Source: NCBI Gene 6725 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 105 total
• Druggable target: yes — 19 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_080823

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11298
Approved symbol	SRMS
Name	src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	SRM, dJ697K14.1, PTK70
Ensembl gene	ENSG00000125508
Ensembl biotype	protein_coding
OMIM	617797
Entrez	6725

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000217188

RefSeq mRNA: 1 — MANE Select: NM_080823 NM_080823

CCDS: CCDS13525

Canonical transcript exons

ENST00000217188 — 8 exons

Exon	Start	End
ENSE00000409757	63541439	63541620
ENSE00000409758	63541191	63541347
ENSE00000663481	63542163	63542321
ENSE00000663482	63542440	63542581
ENSE00000663484	63544227	63544348
ENSE00000663485	63547108	63547749
ENSE00000856597	63543314	63543480
ENSE00001173480	63538489	63540999

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 64.73.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	64.73	gold quality
pancreatic ductal cell	CL:0002079	62.12	silver quality
spleen	UBERON:0002106	59.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	58.63	gold quality
cerebellar hemisphere	UBERON:0002245	58.23	gold quality
parotid gland	UBERON:0001831	58.11	gold quality
cerebellar cortex	UBERON:0002129	57.85	gold quality
transverse colon	UBERON:0001157	57.17	gold quality
ileal mucosa	UBERON:0000331	56.87	silver quality
cerebellum	UBERON:0002037	56.54	gold quality
body of stomach	UBERON:0001161	56.01	gold quality
skin of abdomen	UBERON:0001416	55.79	gold quality
skin of leg	UBERON:0001511	55.68	gold quality
cortical plate	UBERON:0005343	55.42	silver quality
lower esophagus mucosa	UBERON:0035834	55.05	gold quality
epithelial cell of pancreas	CL:0000083	54.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	54.90	gold quality
bone marrow cell	CL:0002092	54.52	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
tibialis anterior	UBERON:0001385	54.33	silver quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
zone of skin	UBERON:0000014	53.67	gold quality
saliva-secreting gland	UBERON:0001044	53.64	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
minor salivary gland	UBERON:0001830	53.28	gold quality
stomach	UBERON:0000945	53.19	gold quality
esophagus mucosa	UBERON:0002469	52.14	gold quality
ventricular zone	UBERON:0003053	51.69	gold quality
mouth mucosa	UBERON:0003729	51.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-1470	98.11	63.53	399
HSA-MIR-340-3P	98.11	68.25	679
HSA-MIR-6742-3P	97.95	64.50	1490

Literature-anchored findings (GeneRIF, showing 4)

• The unique N-terminal region of SRMS regulates enzymatic activity and phosphorylation of its novel substrate docking protein 1. (PMID:23822091)
• SRMS phosphorylated the C terminus of BRK, but not SRC. (PMID:25897081)
• Vimentin and Sam68, are identified as bona fide SRMS substrates through in vitro and in vivo assays. (PMID:29496907)
• The nonreceptor tyrosine kinase SRMS inhibits autophagy and promotes tumor growth by phosphorylating the scaffolding protein FKBP51. (PMID:34077419)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	srms	ENSDARG00000077783
mus_musculus	Srms	ENSMUSG00000027579
rattus_norvegicus	Srms	ENSRNOG00000013003

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Tyrosine-protein kinase Srms — Q9H3Y6 (reviewed: Q9H3Y6)

All UniProt accessions (1): Q9H3Y6

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine-protein kinase which phosphorylates DOK1 on tyrosine residues. Also phosphorylates KHDRBS1/SAM68 and VIM on tyrosine residues. Phosphorylation of KHDRBS1 is EGF-dependent. Phosphorylates OTUB1, promoting deubiquitination of RPTOR.

Subunit / interactions. Interacts (via the SH2 and SH3 domains) with DOK1. Interacts with KHDRBS1/SAM68 and VIM.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in most breast cancers (at protein level).

Domain organisation. The N-terminal region regulates its kinase activity.

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

RefSeq proteins (1): NP_543013* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001452	SH3_domain	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (24 total): sequence variant 13, domain 3, mutagenesis site 3, binding site 2, chain 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3Y6-F1	83.99	0.53

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): 350 (proton acceptor)

Ligand- & substrate-binding residues (2): 236–244; 258

Post-translational modifications (1): 380

Mutagenesis-validated functional residues (3):

Position	Phenotype
223	loss of kinase activity.
258	loss of kinase activity. exhibits a diffused cytoplasmic localization. no effect on interaction with khdrbs1 or vim but
380	significant reduction in phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8849472	PTK6 Down-Regulation
R-HSA-162582	Signal Transduction
R-HSA-8848021	Signaling by PTK6
R-HSA-9006927	Signaling by Non-Receptor Tyrosine Kinases

MSigDB gene sets: 303 (showing top): ELVIDGE_HYPOXIA_DN, GOBP_RESPONSE_TO_PEPTIDE, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, WEI_MYCN_TARGETS_WITH_E_BOX, SCHUHMACHER_MYC_TARGETS_UP, GOBP_POLYAMINE_METABOLIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, KOYAMA_SEMA3B_TARGETS_UP

GO Biological Process (12): cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), negative regulation of signal transduction (GO:0009968), peptidyl-tyrosine phosphorylation (GO:0018108), cell differentiation (GO:0030154), peptidyl-tyrosine autophosphorylation (GO:0038083), positive regulation of TORC1 signaling (GO:1904263), protein phosphorylation (GO:0006468), protein deubiquitination (GO:0016579), cellular response to nutrient levels (GO:0031669), TORC1 signaling (GO:0038202), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of TORC1 signaling (GO:1904262)

GO Molecular Function (9): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by PTK6	1
Signaling by Non-Receptor Tyrosine Kinases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
TORC1 signaling	2
regulation of TORC1 signaling	2
cellular anatomical structure	2
enzyme-linked receptor protein signaling pathway	1
signal transduction	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
protein phosphorylation	1
peptidyl-tyrosine modification	1
cellular developmental process	1
peptidyl-tyrosine phosphorylation	1
protein autophosphorylation	1
positive regulation of TOR signaling	1
phosphorylation	1
protein modification process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
response to nutrient levels	1
cellular response to stimulus	1
TOR signaling	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
negative regulation of TOR signaling	1
protein kinase activity	1
protein tyrosine kinase activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1134 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRMS	TMEM82	A0PJX8	348
SRMS	VGLL2	Q8N8G2	348
SRMS	MYCBPAP	Q8TBZ2	310
SRMS	COPS6	Q7L5N1	286
SRMS	SEC14L4	Q9UDX3	282
SRMS	VSIG8	P0DPA2	276
SRMS	TMEM59L	Q9UK28	261
SRMS	GTPBP10	A4D1E9	259
SRMS	SEC31B	Q9NQW1	253
SRMS	GATA3	P23771	250
SRMS	PPFIA4	O75335	249
SRMS	JSRP1	Q96MG2	247
SRMS	MAL2	Q969L2	246
SRMS	DUSP13B	Q9UII6	244
SRMS	SEL1L3	Q68CR1	242

IntAct

18 interactions, top by confidence:

A	B	Type	Score
DOK1	SRMS	psi-mi:“MI:0217”(phosphorylation reaction)	0.640
SRMS	DOK1	psi-mi:“MI:0915”(physical association)	0.640
DOK1	SRMS	psi-mi:“MI:0915”(physical association)	0.640
NCK2	SRMS	psi-mi:“MI:0915”(physical association)	0.560
HSPB1	SRMS	psi-mi:“MI:0915”(physical association)	0.400
SRMS	ALK	psi-mi:“MI:0915”(physical association)	0.370
SRMS	HAX1	psi-mi:“MI:0914”(association)	0.350
CFAP54	TSPY2	psi-mi:“MI:0914”(association)	0.350
SRMS	TOMM40	psi-mi:“MI:0914”(association)	0.350
SRMS	DUSP14	psi-mi:“MI:0914”(association)	0.350
NCK2	SRMS	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (45): HSPB1 (Affinity Capture-MS), SRMS (Protein-RNA), SKAP2 (PCA), SRMS (Two-hybrid), HSP90AA4P (Affinity Capture-MS), FAM136A (Affinity Capture-MS), HSP90AB3P (Affinity Capture-MS), RBM14-RBM4 (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), KNSTRN (Affinity Capture-MS), CDC37 (Affinity Capture-MS), TOMM40 (Affinity Capture-MS)

ESM2 similar proteins: P00523, P00524, P00525, P00526, P00530, P00541, P00542, P00543, P05480, P06239, P06240, P07332, P08103, P08631, P09769, P12931, P13115, P13116, P14085, P14234, P14238, P15054, P16277, P16879, P23049, P25020, P31693, P41242, P41243, P42679, P42682, P42683, P50545, P51451, P53668, P53669, P55144, P55146, P63185, Q01621

Diamond homologs: A0JNB0, A1A5H8, A1Y2K1, F1LM93, F1RDG9, G5EE56, O45539, P00519, P00520, P00521, P00522, P00523, P00524, P00525, P00526, P00527, P00528, P00544, P03949, P05480, P06239, P06240, P06241, P07947, P07948, P08103, P08630, P08631, P09324, P09769, P10447, P10936, P12931, P13115, P13116, P13406, P14084, P14085, P14234, P15054

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SRMS	unknown	DOK1	phosphorylation
SRMS	“down-regulates quantity by destabilization”	FKBP5	phosphorylation
SRMS	“down-regulates activity”	MAP2K4	phosphorylation
SRMS	“down-regulates activity”	FKBP4	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1602 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63541438:C:G	donor_loss	1.0000
20:63541621:C:CC	acceptor_gain	1.0000
20:63542161:A:AC	donor_gain	1.0000
20:63542161:ACTG:A	donor_gain	1.0000
20:63542161:ACTGC:A	donor_gain	1.0000
20:63542162:C:CC	donor_gain	1.0000
20:63542162:CTG:C	donor_gain	1.0000
20:63542162:CTGC:C	donor_gain	1.0000
20:63542162:CTGCC:C	donor_gain	1.0000
20:63543355:T:TA	donor_gain	1.0000
20:63543481:C:CC	acceptor_gain	1.0000
20:63547106:A:AC	donor_gain	1.0000
20:63547107:C:CC	donor_gain	1.0000
20:63541184:GACCC:G	donor_loss	0.9900
20:63541185:ACCC:A	donor_loss	0.9900
20:63541186:CCCA:C	donor_loss	0.9900
20:63541187:CCA:C	donor_loss	0.9900
20:63541344:CGTC:C	acceptor_gain	0.9900
20:63541346:TCCTG:T	acceptor_loss	0.9900
20:63541347:CCT:C	acceptor_loss	0.9900
20:63541348:C:CC	acceptor_gain	0.9900
20:63541348:C:CG	acceptor_loss	0.9900
20:63541355:C:CT	acceptor_gain	0.9900
20:63541437:A:AC	donor_gain	0.9900
20:63541438:C:CC	donor_gain	0.9900
20:63541616:GGGGG:G	acceptor_gain	0.9900
20:63541617:GGGG:G	acceptor_gain	0.9900
20:63541618:GGG:G	acceptor_gain	0.9900
20:63541618:GGGC:G	acceptor_loss	0.9900
20:63541620:GC:G	acceptor_loss	0.9900

AlphaMissense

3140 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63541302:A:G	W392R	0.992
20:63541302:A:T	W392R	0.992
20:63542453:C:A	K258N	0.991
20:63542453:C:G	K258N	0.991
20:63541463:G:C	D368E	0.990
20:63541463:G:T	D368E	0.990
20:63541248:A:G	W410R	0.987
20:63541248:A:T	W410R	0.987
20:63541515:A:G	L351S	0.987
20:63541517:G:C	D350E	0.985
20:63541517:G:T	D350E	0.985
20:63541518:T:G	D350A	0.985
20:63542207:A:T	V301D	0.985
20:63541300:C:A	W392C	0.984
20:63541300:C:G	W392C	0.984
20:63541472:C:A	K365N	0.983
20:63541472:C:G	K365N	0.983
20:63541518:T:A	D350V	0.983
20:63542504:A:C	F241L	0.983
20:63542504:A:T	F241L	0.983
20:63542506:A:G	F241L	0.983
20:63541238:C:T	G413D	0.981
20:63541521:C:G	R349P	0.980
20:63544273:G:C	F144L	0.980
20:63544273:G:T	F144L	0.980
20:63544275:A:G	F144L	0.980
20:63541295:G:T	A394E	0.979
20:63541518:T:C	D350G	0.979
20:63541464:T:A	D368V	0.976
20:63541303:C:A	K391N	0.974

dbSNP variants (sampled 300 via entrez): RS1000288768 (20:63541688 C>T), RS1000411296 (20:63545749 C>A,T), RS1000484792 (20:63546044 CT>C), RS1000749498 (20:63544745 C>G), RS1000841736 (20:63549235 CCGA>C), RS1000987844 (20:63547823 G>A), RS1001072609 (20:63539749 C>T), RS1001505468 (20:63539522 C>G), RS1001812833 (20:63540095 TG>T,TGG), RS1002117873 (20:63548358 T>C), RS1002149052 (20:63548687 G>A), RS1002449850 (20:63542838 G>T), RS1002588512 (20:63547508 G>A,C), RS1002957183 (20:63546728 C>T), RS1003336527 (20:63549643 C>T)

Disease associations

OMIM: gene MIM:617797 | disease phenotypes: MIM:256730

GenCC curated gene-disease

Mondo (2): neuronal ceroid lipofuscinosis (MONDO:0016295), developmental and epileptic encephalopathy (MONDO:0100620)

Orphanet (2): Neuronal ceroid lipofuscinosis (Orphanet:216), OBSOLETE: Infantile neuronal ceroid lipofuscinosis (Orphanet:79263)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001942_22	Prostate cancer	4.000000e-16
GCST004521_202	Autism spectrum disorder or schizophrenia	4.000000e-08
GCST008103_74	Bipolar disorder	8.000000e-07
GCST008115_28	Bipolar I disorder	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009963	bipolar I disorder

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363074 (PROTEIN FAMILY), CHEMBL5703 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 208,958 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL5416410	DASATINIB	4	655
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL1738757	REBASTINIB	2	1,478
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL215152	DEFOSBARASERTIB	2	372
CHEMBL253969	OSI-632	2	1,150
CHEMBL475251	R-406	2	762
CHEMBL1908397	KW-2449	1	622
CHEMBL574738	AST-487	1	451

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Src family

Binding affinities (BindingDB)

10 measured of 10 human assays (10 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
BMS-354825	KD	27 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CI-1033	KD	1700 nM
2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide	KD	1900 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM

ChEMBL bioactivities

111 potent at pChembl≥5 of 112 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.20	Ki	0.631	nM	DASATINIB
8.20	Ki	6.31	nM	CHEMBL1997617
8.10	IC50	8	nM	CHEMBL4108687
8.04	IC50	9.1	nM	CHEMBL4106978
7.89	Kd	13	nM	DASATINIB
7.85	IC50	14	nM	CHEMBL4749037
7.80	IC50	16	nM	CHEMBL4114929
7.75	Kd	18	nM	FORETINIB
7.72	IC50	19	nM	CHEMBL4076024
7.68	Kd	21	nM	PLX-4720
7.64	IC50	23	nM	CHEMBL4103954
7.62	IC50	24	nM	CHEMBL4799627
7.60	Ki	25.12	nM	CHEMBL2006715
7.60	Ki	25.12	nM	CHEMBL2004716
7.60	Ki	25.12	nM	ILORASERTIB
7.55	Kd	28	nM	CHEMBL5415503
7.50	IC50	32	nM	CHEMBL4094125
7.30	IC50	50	nM	CHEMBL4077588
7.30	Ki	50.12	nM	CHEMBL1988387
7.30	Ki	50.12	nM	CHEMBL1981047
7.21	IC50	61	nM	CHEMBL4107779
7.21	Kd	62	nM	SU-014813
7.19	Kd	64	nM	CHEMBL4098896
7.19	IC50	65	nM	CHEMBL4060757
7.14	Kd	72	nM	AST-487
7.12	IC50	76	nM	CHEMBL4062498
7.10	Ki	79.43	nM	CHEMBL508928
7.08	IC50	84	nM	CHEMBL4069387
7.00	Kd	100	nM	BOSUTINIB
7.00	Ki	100	nM	CHEMBL1993661
6.99	IC50	103	nM	CHEMBL4075954
6.94	IC50	114	nM	CHEMBL4862806
6.90	Ki	125.9	nM	CHEMBL1989708
6.90	Ki	125.9	nM	CHEMBL1996979
6.90	Ki	125.9	nM	CHEMBL1972584
6.80	Kd	160	nM	TAE-684
6.80	Ki	158.5	nM	CHEMBL2005886
6.80	Ki	158.5	nM	CHEMBL1994938
6.70	Ki	199.5	nM	CHEMBL1981725
6.70	Ki	199.5	nM	CHEMBL1968590
6.70	Ki	199.5	nM	CHEMBL1990821
6.70	Ki	199.5	nM	CHEMBL1967720
6.60	Ki	251.2	nM	CHEMBL1987034
6.60	Ki	251.2	nM	CHEMBL2002165
6.50	Ki	316.2	nM	TAE-684
6.50	Ki	316.2	nM	CHEMBL1993941
6.43	IC50	370	nM	REBASTINIB
6.40	Kd	400	nM	CHEMBL1908396
6.40	Ki	398.1	nM	CHEMBL1982924
6.40	Ki	398.1	nM	CHEMBL2004311

PubChem BioAssay actives

57 with measured affinity, of 776 total; 39 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
4-[3-[(6R,8aS)-1,1-dimethyl-3-oxo-6,7,8,8a-tetrahydro-5H-[1,3]oxazolo[3,4-a]pyridin-6-yl]-8-aminoimidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721758: Inhibition of SRMS (unknown origin)	ic50	0.0080	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721758: Inhibition of SRMS (unknown origin)	ic50	0.0091	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	435561: Binding constant for SRMS kinase domain	kd	0.0130	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-1,5,6,7,8,8a-hexahydro-[1,3]oxazolo[3,4-a]pyridin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721758: Inhibition of SRMS (unknown origin)	ic50	0.0140	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-3-methoxy-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721758: Inhibition of SRMS (unknown origin)	ic50	0.0160	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	624710: Binding constant for SRMS kinase domain	kd	0.0180	uM
4-[8-amino-3-[(3R)-1-(2-methoxyacetyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488594: Inhibition of SRMS (unknown origin)	ic50	0.0190	uM
N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide	624710: Binding constant for SRMS kinase domain	kd	0.0210	uM
4-[8-amino-3-[(3R,6S)-1-(cyclopropanecarbonyl)-6-methylpiperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711665: Inhibition of human SRMS	ic50	0.0230	uM
4-[8-amino-3-[(3R)-1-(3-methyloxetane-3-carbonyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711665: Inhibition of human SRMS	ic50	0.0240	uM
N-[3-[2-[2-ethoxy-4-(4-methylpiperazin-1-yl)anilino]-7-oxo-8-[[(2R)-oxolan-2-yl]methyl]pyrido[2,3-d]pyrimidin-6-yl]phenyl]-3-(trifluoromethyl)benzamide	1988553: Binding affinity to SRMS (unknown origin) assessed as dissociation constant by KINOME scan assay	kd	0.0280	uM
4-[8-amino-3-[(3R)-1-(3-methyloxetane-3-carbonyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711665: Inhibition of human SRMS	ic50	0.0320	uM
4-[8-amino-3-[(3R)-1-(oxan-4-yl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488594: Inhibition of SRMS (unknown origin)	ic50	0.0500	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-3-cyclopropyloxy-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721758: Inhibition of SRMS (unknown origin)	ic50	0.0610	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435561: Binding constant for SRMS kinase domain	kd	0.0620	uM
3-cyano-N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486196: Binding affinity to partial length human SRMS expressed in HEK293 cells by active-site-dependent competition assay	kd	0.0640	uM
4-[8-amino-3-[(2R)-4-(oxan-4-yl)morpholin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488594: Inhibition of SRMS (unknown origin)	ic50	0.0650	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435561: Binding constant for SRMS kinase domain	kd	0.0720	uM
4-[8-amino-3-[(2R)-4-(2-methoxyacetyl)morpholin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488594: Inhibition of SRMS (unknown origin)	ic50	0.0760	uM
4-[8-amino-3-[(3R)-1-(2-methylpropanoyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488594: Inhibition of SRMS (unknown origin)	ic50	0.0840	uM
Bosutinib	624710: Binding constant for SRMS kinase domain	kd	0.1000	uM
4-[8-amino-3-[(2R)-4-(2-methylpropanoyl)morpholin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488594: Inhibition of SRMS (unknown origin)	ic50	0.1030	uM
3-[2-[2-amino-5-(1-methylpyrazol-4-yl)-3-pyridinyl]ethynyl]-N-[3,5-bis(trifluoromethyl)phenyl]-4-methylbenzamide	1780020: Inhibition of human SRMS by radiometric scintillation counting analysis	ic50	0.1140	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624710: Binding constant for SRMS kinase domain	kd	0.1600	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168261: Inhibition of human wild type SRMS using PolyEY as substrate preincubated for 2 hrs followed by ATP addition and measured every 2 mins for 2.5 hrs by spectrophotometric analysis	ic50	0.3700	uM
1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-methoxyphenyl]-3-[1-(1,3-thiazol-2-yl)ethyl]urea	624710: Binding constant for SRMS kinase domain	kd	0.4000	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624710: Binding constant for SRMS kinase domain	kd	0.6000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624710: Binding constant for SRMS kinase domain	kd	0.6100	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	435561: Binding constant for SRMS kinase domain	kd	0.7400	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	508090: Binding affinity to SRMS	kd	0.8200	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	435561: Binding constant for SRMS kinase domain	kd	1.4000	uM
Vandetanib	435561: Binding constant for SRMS kinase domain	kd	1.9000	uM
Pazopanib	435561: Binding constant for SRMS kinase domain	kd	2.5000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624710: Binding constant for SRMS kinase domain	kd	2.7000	uM
Fedratinib	624710: Binding constant for SRMS kinase domain	kd	5.0000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	435561: Binding constant for SRMS kinase domain	kd	6.7000	uM
2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide	435561: Binding constant for SRMS kinase domain	kd	7.9000	uM
1-tert-butyl-3-(4-chlorophenyl)pyrazolo[3,4-d]pyrimidin-4-amine	2196721: Inhibition of Src family in bortezomib Resistant human RPMI-8226 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay	ic50	9.5509	uM
Sorafenib	435561: Binding constant for SRMS kinase domain	kd	9.8000	uM

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol A	increases expression	1
sodium arsenite	increases expression	1
tebuconazole	decreases expression	1
Diazinon	increases methylation	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

179 unique, capped per target: 178 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5719121	Binding	Inhibition of Src family in human RPMI-8226 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay	Small molecule inhibitor screen identifies synergistic activity of the bromodomain inhibitor CPI203 and bortezomib in drug resistant myeloma. — Oncotarget
CHEMBL1963770	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: SRMS	PubChem BioAssay data set

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT00337636	PHASE1	COMPLETED	Study of HuCNS-SC Cells in Patients With Infantile or Late Infantile Neuronal Ceroid Lipofuscinosis (NCL)
NCT01238315	PHASE1	WITHDRAWN	Safety and Efficacy Study of HuCNS-SC in Subjects With Neuronal Ceroid Lipofuscinosis
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT07582484	PHASE1/PHASE2	NOT_YET_RECRUITING	Gene Therapy Trial for CLN6 Batten Disease
NCT01873924	Not specified	RECRUITING	Clinical and Neuropsychological Investigations in Batten Disease
NCT01966757	Not specified	COMPLETED	Neuronal Ceroid Lipofuscinosis and Associated Sleep Abnormalities
NCT04613089	Not specified	RECRUITING	Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database
NCT06844877	Not specified	RECRUITING	Italian NCL Registry: a Registry for NCL as an Integration Tool for Future Therapeutic Strategies
NCT03876444	PHASE2/PHASE3	UNKNOWN	Intravenous Methylprednisolone Versus Oral Prednisolone for Infantile Spasms
NCT05279118	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT04302116	Not specified	RECRUITING	Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
NCT05538936	Not specified	COMPLETED	The Effect of Spa and Massage on Babies on Colic Symptoms
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06266234	Not specified	RECRUITING	Characterization by Automated System on Infantile Spasmes
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07413211	Not specified	RECRUITING	Genetic Developmental and Epileptic Encephalopathy Natural History Study for Clinical Trial Readiness
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).