FRK

Summary

FRK (fyn related Src family tyrosine kinase, HGNC:3955) is a protein-coding gene on chromosome 6q22.1, encoding Tyrosine-protein kinase FRK (P42685). Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation.

The protein encoded by this gene belongs to the TYR family of protein kinases. This tyrosine kinase is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth.

Source: NCBI Gene 2444 — RefSeq curated summary.

At a glance

• GWAS associations: 41 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 60 total
• GTEx eGene: eQTL in 40 tissues, sQTL in 2 (q < 0.05)
• Drug target: yes — 1 curated mechanism-of-action drug, 5 via a complex or family; 71 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 1 — Regorafenib
• Approved drugs acting on a complex or family including it: 1 — Dasatinib Anhydrous (SRC)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.02 (unconstrained)
• MANE Select transcript: NM_002031
• Notable: 60 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3955
Approved symbol	FRK
Name	fyn related Src family tyrosine kinase
Location	6q22.1
Locus type	gene with protein product
Status	Approved
Aliases	RAK, GTK
Ensembl gene	ENSG00000111816
Ensembl biotype	protein_coding
OMIM	606573
Entrez	2444

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

MANE Select: ENST00000606080

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000606080, ENST00000891226, ENST00000891227, ENST00000891228, ENST00001141083

RefSeq mRNA: 1 — MANE Select: NM_002031 NM_002031

CCDS: CCDS5103

Canonical transcript exons

ENST00000606080 — 8 exons

Exon	Start	End
ENSE00000762579	116003877	116003998
ENSE00000762581	115968576	115968739
ENSE00000762582	115967551	115967719
ENSE00000762585	115956452	115956610
ENSE00000762586	115944244	115944425
ENSE00000762607	115943020	115943185
ENSE00001447601	116059968	116060891
ENSE00003696238	115931149	115942625

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 92.78.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6303 / max 64.2603, expressed in 425 samples.

Highest expression (Bgee): jejunal mucosa, mucosa of sigmoid colon, colonic mucosa, esophagus squamous epithelium, epithelium of nasopharynx.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FRK is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 40 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 42 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	1.1e-46	-0.44	6:116052453:C:T
Cells Cultured fibroblasts	eqtl	2.3e-35	-0.35	6:116060831:T:C
Artery Aorta	eqtl	2.5e-23	+0.35	6:115920421:G:A
Artery Tibial	eqtl	2.6e-23	+0.32	6:115922231:A:G
Pancreas	eqtl	7.6e-23	-0.44	6:116025231:C:A
Esophagus Muscularis	eqtl	2.3e-22	-0.44	6:116060831:T:C
Thyroid	eqtl	1.3e-15	-0.27	6:116061554:T:TACTA
Esophagus Gastroesophageal Junction	eqtl	9.1e-15	-0.40	6:116060831:T:C
Skin Not Sun Exposed Suprapubic	eqtl	8.3e-14	+0.26	6:115922231:A:G
Adrenal Gland	eqtl	2.9e-12	-0.46	6:116078298:GT:G
Cells EBV-transformed lymphocytes	eqtl	1.0e-11	+0.38	6:116001186:C:T
Stomach	eqtl	1.0e-09	-0.20	6:116061554:T:TACTA
Brain Spinal cord cervical c-1	eqtl	5.4e-09	-1.48	6:116049117:T:C
Brain Cortex	eqtl	6.3e-09	-1.58	6:116049117:T:C
Adipose Visceral Omentum	eqtl	2.9e-08	-0.19	6:116061554:T:TACTA
Pituitary	eqtl	8.7e-08	-0.45	6:116093406:T:C
Colon Transverse	eqtl	1.0e-07	+0.13	6:116096949:G:A
Skin Sun Exposed Lower leg	eqtl	1.2e-07	+0.18	6:115918718:T:C
Heart Atrial Appendage	eqtl	3.6e-06	-0.28	6:116100391:C:T
Nerve Tibial	eqtl	4.2e-06	-0.16	6:115966974:A:AG

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
75236	0.7555	317
75234	0.6532	250
75235	0.2215	130

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	92.78	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.60	gold quality
colonic mucosa	UBERON:0000317	90.28	gold quality
esophagus squamous epithelium	UBERON:0006920	88.37	gold quality
epithelium of nasopharynx	UBERON:0001951	88.13	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.75	gold quality
bronchial epithelial cell	CL:0002328	85.48	gold quality
buccal mucosa cell	CL:0002336	84.64	gold quality
palpebral conjunctiva	UBERON:0001812	83.13	gold quality
epithelium of esophagus	UBERON:0001976	82.09	gold quality
parotid gland	UBERON:0001831	81.87	gold quality
sperm	CL:0000019	80.81	gold quality
corpus epididymis	UBERON:0004359	80.72	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	80.61	gold quality
heart right ventricle	UBERON:0002080	80.01	gold quality
duodenum	UBERON:0002114	78.96	gold quality
caput epididymis	UBERON:0004358	78.83	gold quality
oral cavity	UBERON:0000167	78.80	gold quality
epithelium of bronchus	UBERON:0002031	78.59	gold quality
squamous epithelium	UBERON:0006914	78.50	gold quality
male germ cell	CL:0000015	78.24	silver quality
seminal vesicle	UBERON:0000998	78.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.06	silver quality
gingival epithelium	UBERON:0001949	78.01	gold quality
bronchus	UBERON:0002185	77.94	gold quality
visceral pleura	UBERON:0002401	77.32	gold quality
ileal mucosa	UBERON:0000331	77.12	silver quality
tendon of biceps brachii	UBERON:0008188	76.32	silver quality
gingiva	UBERON:0001828	76.30	gold quality
islet of Langerhans	UBERON:0000006	76.08	gold quality
amniotic fluid	UBERON:0000173	75.92	gold quality
liver	UBERON:0002107	75.54	gold quality
descending thoracic aorta	UBERON:0002345	75.40	gold quality
right coronary artery	UBERON:0001625	75.36	gold quality
superficial temporal artery	UBERON:0001614	74.80	gold quality
germinal epithelium of ovary	UBERON:0001304	74.69	gold quality
jejunum	UBERON:0002115	74.66	gold quality
adult mammalian kidney	UBERON:0000082	74.57	gold quality
popliteal artery	UBERON:0002250	74.50	gold quality
tibial artery	UBERON:0007610	74.44	gold quality
endothelial cell	CL:0000115	74.41	silver quality
cauda epididymis	UBERON:0004360	74.29	gold quality
lower lobe of lung	UBERON:0008949	74.17	silver quality
pleura	UBERON:0000977	73.99	gold quality
rectum	UBERON:0001052	73.98	gold quality
nasal cavity mucosa	UBERON:0001826	73.74	gold quality
parietal pleura	UBERON:0002400	73.71	gold quality
aorta	UBERON:0000947	73.51	gold quality
nasal cavity epithelium	UBERON:0005384	73.40	gold quality
left coronary artery	UBERON:0001626	73.15	gold quality
coronary artery	UBERON:0001621	72.83	gold quality
kidney	UBERON:0002113	72.72	gold quality
biceps brachii	UBERON:0001507	72.70	gold quality
tendon	UBERON:0000043	72.58	gold quality
mucosa of transverse colon	UBERON:0004991	72.58	gold quality
mammary duct	UBERON:0001765	72.57	gold quality
right lobe of liver	UBERON:0001114	72.42	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.42	gold quality
thoracic aorta	UBERON:0001515	72.19	gold quality
ascending aorta	UBERON:0001496	71.80	gold quality
renal medulla	UBERON:0000362	71.72	gold quality
colonic epithelium	UBERON:0000397	71.19	gold quality
epithelium of mammary gland	UBERON:0003244	71.07	gold quality
tonsil	UBERON:0002372	70.74	gold quality
pancreas	UBERON:0001264	70.73	gold quality
esophagus mucosa	UBERON:0002469	70.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	69.88	gold quality
blood vessel layer	UBERON:0004797	69.66	gold quality
oviduct epithelium	UBERON:0004804	69.26	gold quality
saliva-secreting gland	UBERON:0001044	69.11	gold quality
calcaneal tendon	UBERON:0003701	68.59	gold quality
adrenal tissue	UBERON:0018303	68.43	gold quality
cardiac ventricle	UBERON:0002082	68.34	gold quality
heart left ventricle	UBERON:0002084	68.13	gold quality
endometrium	UBERON:0001295	67.97	gold quality
body of pancreas	UBERON:0001150	67.84	gold quality
saphenous vein	UBERON:0007318	67.55	gold quality
mouth mucosa	UBERON:0003729	67.49	gold quality
minor salivary gland	UBERON:0001830	67.48	gold quality
lower esophagus mucosa	UBERON:0035834	67.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	67.08	gold quality
epithelial cell of pancreas	CL:0000083	67.06	gold quality
gall bladder	UBERON:0002110	66.99	gold quality
mammary gland	UBERON:0001911	66.82	gold quality
metanephros cortex	UBERON:0010533	66.78	gold quality
thoracic mammary gland	UBERON:0005200	66.76	gold quality
heart	UBERON:0000948	66.61	gold quality
upper leg skin	UBERON:0004262	66.13	gold quality
small intestine	UBERON:0002108	66.05	gold quality
myocardium	UBERON:0002349	65.86	silver quality
pancreatic ductal cell	CL:0002079	65.77	silver quality
urinary bladder	UBERON:0001255	65.40	gold quality
fallopian tube	UBERON:0003889	65.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	65.26	gold quality
skin of hip	UBERON:0001554	65.20	gold quality
transverse colon	UBERON:0001157	65.19	gold quality
stomach	UBERON:0000945	65.07	gold quality
cortex of kidney	UBERON:0001225	65.05	gold quality
vastus lateralis	UBERON:0001379	64.77	silver quality
skeletal muscle tissue	UBERON:0001134	64.61	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	3523.97
E-MTAB-6678	yes	1845.49
E-GEOD-130473	yes	962.52
E-CURD-97	yes	497.81
E-MTAB-7008	yes	239.84
E-ANND-3	yes	6.15
E-MTAB-9067	no	1442.30
E-MTAB-7249	no	425.12
E-MTAB-7381	no	305.63
E-ENAD-20	no	146.09
E-GEOD-70580	no	84.72

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 71 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	59.6
Postcentral gyrus	tissue	39.0
Hippocampus	tissue	29.8	not detected
Nucleus accumbens	tissue	29.4
Locus coeruleus	tissue	24.2
Kidney	tissue	8.4	high
Liver	tissue	6.2	high
Small intestine	tissue	5.9	high
Duodenum	tissue	5.8	high
Stomach 1	tissue	4.6	medium
Rectum	tissue	4.5	low
Colon	tissue	4.3	low
Salivary gland	tissue	3.7	low
Pancreas	tissue	2.5	not detected
Retina	tissue	2.4
Esophagus	tissue	2.4	not detected
Gallbladder	tissue	2.4	not detected
Fallopian tube	tissue	2.4	not detected
Epididymis	tissue	2.3	not detected
Breast	tissue	2.2	not detected
Seminal vesicle	tissue	2.2	medium
Prostate	tissue	2.1	not detected
Skeletal muscle	tissue	2.0	not detected
Urinary bladder	tissue	1.9	not detected
Skin 1	tissue	1.7	not detected
Testis	tissue	1.7	medium
Lung	tissue	1.7	not detected
Cervix	tissue	1.6	not detected
Heart muscle	tissue	1.5	low
Tonsil	tissue	1.5	not detected
Bone marrow	tissue	1.2	not detected
Thymus	tissue	1.1
Appendix	tissue	1.1	not detected
Vagina	tissue	1.0	not detected
Adrenal gland	tissue	1.0	medium
Parathyroid gland	tissue	0.9	medium
Endometrium 1	tissue	0.9	low
Thyroid gland	tissue	0.9	not detected
Smooth muscle	tissue	0.8	medium
Placenta	tissue	0.8	not detected
Spleen	tissue	0.8	not detected
Adipose tissue	tissue	0.7	not detected
Tongue	tissue	0.7
Lymph node	tissue	0.6	not detected
Ovary	tissue	0.6	medium
Pituitary gland	tissue	0.3
Frontal cortex	tissue	0.3
Basal ganglia	tissue	0.3	not detected
Putamen	tissue	0.3
Cerebral cortex	tissue	0.2	not detected
Superior colliculi	tissue	0.2
Ventral forebrain	tissue	0.2
Septum	tissue	0.2
Caudate putamen	tissue	0.2
Somatosensory cortex	tissue	0.2
Prefrontal cortex	tissue	0.1
Pons	tissue	0.1
Motor cortex	tissue	0.1
Midbrain	tissue	0.1
Medulla oblongata	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 186; highest nTPM — Vermis (40.3), Flocculonodular lobe (39.4), Somatosensory cortex, postcentral gyrus, ventral (white matter) (39.1), Somatomor cortex, precentral gyrus (white matter) (38.8), Parietal operculum (38.7).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
TERT	Repression

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

Targeting FRK by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 97 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-3P	99.82	70.56	3549

Functional genomics

gnomAD constraint: pLI 1.26e-13, LOEUF 1.02, missense Z 1.06 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000606080 — one region, missense o/e 0.95.

Literature-anchored findings (GeneRIF, showing 26)

• Breast cancer cell line proliferation blocked by the Src-related Rak tyrosine kinase (PMID:12569567)
• The tyrosine kinases Brk/PTK6/Sik, Srm, Frk/Rak/Gtk/Iyk/Bsk, and Src42A/Dsrc41 have a low degree of sequence homology to other known kinases. The exon structure of these kinases, called the Brk family, is highly conserved and distinct. (PMID:12725532)
• Three common Japanese polymorphisms of the Fyn kinase gene studied in 127 healthy controls and 182 sporadic Alzheimer’s disease failed to demonstrate any significant difference. (PMID:15082191)
• Rak functions as a tumor suppressor by regulating PTEN protein stability and function in breast and bone neoplasms. (PMID:19345329)
• Study searched for mutations in the FRK gene, a recently identified tumor suppressor gene, for the first time in NSCLC. Somatic FRK mutations were found at a very low frequency in NSCLCs. (PMID:21074287)
• Genetic variation near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. (PMID:21665990)
• these results clearly indicate that FRK may play a protective role against the progression of glioma by suppressing cell migration and invasion (PMID:22790444)
• The expression levels of FRK were significantly correlated with invasiveness in both Hep3B and HepG2 tumor cell lines. (PMID:23267173)
• Data indicaate that the Rak/Frk SH2 and SH3 domains collaborate to increase the Rak-EGFR interaction. (PMID:23318459)
• exome sequencing identified recurrent somatic FRK mutations that induce constitutive kinase activity, STAT3 activation, and cell proliferation sensitive to Src inhibitors (PMID:24735922)
• our results demonstrate a combined mechanism for the anti-proliferative effects of FRK by inhibiting cyclin D1 nucleus accumulation and pRb phosphorylation in glioma cells. (PMID:24792491)
• FRK over-expression promoted beta-catenin translocation to the plasma membrane, where it formed complex with N-cadherin. (PMID:24969324)
• antagomir-1290 significantly inhibited the proliferation, clonogenicity, invasion, and migration of CD133(+) cells by targeting fyn-related Src family tyrosine kinase. (PMID:25783528)
• Loss of FRK protein may be implicated into the tumorigenesis and cell motility/invasiveness of human cervical cancer. (PMID:27665472)
• our results present the first evidence that site-specific promoter methylation contributes to the repression of FRK more so in basal B breast cancers. (PMID:28077797)
• Targetable fusions of the FRK tyrosine kinase in ALK-negative anaplastic large cell lymphoma. (PMID:29026208)
• FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes epithelial-mesenchymal transition and metastasis (PMID:31251822)
• These results indicate that FRK inhibits human glioma growth via regulating ITGB1/FAK signaling. (PMID:31395336)
• Activated BRK-mediated degradation of SMAD4 is associated with the repression of tumor suppressor gene FRK. (PMID:31681835)
• TRIM44 promotes cell proliferation by regulating FRK. (PMID:31883420)
• Down-Regulation of miR-2053 Inhibits the Development and Progression of Esophageal Carcinoma by Targeting Fyn-Related Kinase (FRK). (PMID:31894485)
• Recurrent chromosomal rearrangements of ROS1, FRK and IL6 activating JAK/STAT pathway in inflammatory hepatocellular adenomas. (PMID:31907296)
• Furry protein suppresses nuclear localization of yes-associated protein (YAP) by activating NDR kinase and binding to YAP. (PMID:31996378)
• GATA6 activated long non-coding RNA PCAT1 maintains stemness of non-small cell lung cancer by mediating FRK. (PMID:33277858)
• FRK inhibits glioblastoma progression via phosphorylating YAP and inducing its ubiquitylation and degradation by Siah1. (PMID:35723276)
• Hemifacial microsomia is linked to a rare homozygous variant V162I in FRK and validated in zebrafish. (PMID:36070195)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	frk	ENSDARG00000027807
mus_musculus	Frk	ENSMUSG00000019779
rattus_norvegicus	Frk	ENSRNOG00000000543

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), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), 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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:103265) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating triiodothyronine level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	P00523	100.0%	Diamond
Coturnix japonica	P34908	100.0%	Diamond
Drosophila melanogaster	Q08012	100.0%	Diamond
Bos taurus	A0JNB0	99.6%	Diamond
Sus scrofa	A1Y2K1	99.4%	Diamond
Felis catus	P14238	98.7%	Diamond
Xenopus laevis	P87379	98.7%	Diamond
Calliphora vicina	P11681	98.6%	Diamond
Canis lupus familiaris	A0A8I3NFE2	95.9%	Diamond
Avian retrovirus IC10	P10533	100.0%	Diamond
Avian sarcoma virus PR2257	P15054	100.0%	Diamond
Rous-associated virus type 1	P27966	100.0%	Diamond
Avian sarcoma virus S2	P14085	99.8%	Diamond
Avian sarcoma virus S1	P14084	99.6%	Diamond
Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 2)	P10447	99.3%	Diamond
Gardner-Arnstein feline sarcoma virus	P00542	99.1%	Diamond
Snyder-Theilen feline sarcoma virus	P00543	99.1%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin A)	P00524	99.0%	Diamond
Avian sarcoma virus RASV1441	P00525	99.0%	Diamond
Rous sarcoma virus - Prague C	P00526	99.0%	Diamond
Rous sarcoma virus (strain H-19)	P25020	99.0%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin E)	P63185	99.0%	Diamond
Y73 sarcoma virus	P00527	98.9%	Diamond
Avian carcinoma Mill Hill virus 2	P00531	98.9%	Diamond
Murine sarcoma virus 3611	P00532	98.8%	Diamond
Abelson murine leukemia virus	P00521	98.7%	Diamond
Rous sarcoma virus (strain PA101T)	P31693	95.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
COL10A1	protein-coding	1300
NT5DC1	protein-coding	221294
TSPYL4	protein-coding	23270
DSE	protein-coding	29940
LINC02534	ncRNA	105377962
TSPYL1	protein-coding	7259

Protein

Protein identifiers

Tyrosine-protein kinase FRK — P42685 (reviewed: P42685)

Alternative names: FYN-related kinase, Nuclear tyrosine protein kinase RAK, Protein-tyrosine kinase 5

All UniProt accessions (1): P42685

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on ‘Tyr-336’, which in turn prevents its ubiquitination and degradation, possibly by reducing its binding to NEDD4. May function as a tumor suppressor.

Subunit / interactions. Interacts (via the SH3-domain) with PTEN. Interacts with RB1.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Predominantly expressed in epithelial derived cell lines and tissues, especially normal liver, kidney, breast and colon.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P42685-1	1	yes
P42685-2	2

RefSeq proteins (1): NP_002022* (*=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
IPR035805	SH2_Frk	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00018, 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)

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

UniProt features (18 total): modified residue 4, domain 3, sequence variant 3, splice variant 2, binding site 2, chain 1, mutagenesis site 1, sequence conflict 1, active site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42685-F1	83.41	0.60

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Predicted intracellular proteins, Plasma proteins, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
354	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
240–248	ATP
262	ATP

Post-translational modifications (4)

Type	Positions
Phosphotyrosine	387
Phosphoserine	37, 40
Phosphothreonine	178

Mutagenesis-validated functional residues (1)

Position	Phenotype
262	loss of ability to phosphorylate pten.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-8948751	Regulation of PTEN stability and activity	curated
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-1257604	PIP3 activates AKT signaling	—
R-HSA-6807070	PTEN Regulation	—
R-HSA-162582	Signal Transduction	—

MSigDB gene sets: 134 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOZGIT_ESR1_TARGETS_DN, AAGCCAT_MIR135A_MIR135B, CAGCAGG_MIR370, MORF_EPHA7, DOUGLAS_BMI1_TARGETS_DN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, CUI_TCF21_TARGETS_2_DN, GOMF_SIGNALING_RECEPTOR_BINDING, WALLACE_PROSTATE_CANCER_RACE_DN, RIGGI_EWING_SARCOMA_PROGENITOR_UP, MORF_IL9, MORF_DCC, GOCC_SECRETORY_VESICLE

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), cell differentiation (GO:0030154), protein phosphorylation (GO:0006468)

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 (9): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), azurophil granule lumen (GO:0035578), specific granule lumen (GO:0035580), extracellular exosome (GO:0070062)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Innate Immune System	1
PTEN Regulation	1
Intracellular signaling by second messengers	1
Immune System	1
PIP3 activates AKT signaling	1
Signal Transduction	1

GO top-level categories

33 GO namespaces:

Category	Terms
cellular anatomical structure	4
secretory granule lumen	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
enzyme-linked receptor protein signaling pathway	1
cellular developmental process	1
phosphorylation	1
protein modification process	1
protein kinase activity	1
protein tyrosine kinase activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion 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 membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
vacuolar lumen	1
azurophil granule	1
specific granule	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of transcription by RNA polymerase II	BP	direct assay
cytoplasm	CC	direct assay
extracellular exosome	CC	high-throughput assay
nucleoplasm	CC	direct assay
protein tyrosine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 699 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FRK	RAPGEF1	Q13905	827
FRK	RASGRF2	O14827	760
FRK	UGP2	Q16851	573
FRK	TK1	P04183	561
FRK	CRK	P46108	558
FRK	GPI	P06744	522
FRK	COL10A1	Q03692	436
FRK	NGF	P01138	408
FRK	EEIG2	Q5T8I3	373
FRK	SH2D1B	O14796	370
FRK	HSD17B10	Q99714	360
FRK	PSMD4	P55036	360
FRK	SH2D1A	O60880	357
FRK	COL15A1	P39059	352
FRK	B3GLCT	Q6Y288	347

IntAct

Human interaction partners of FRK in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

14 partners by confidence:

Partner	Interaction type	MIscore	Records
BNIP2	physical association	0.830	8
SF3B4	physical association	0.670	4
PTEN	physical association	0.640	7
CSK	association	0.640	1
EGFR	physical association	0.550	2
RB1	direct interaction	0.540	3
ABI1	direct interaction	0.440	1
HSP90AB1	physical association	0.400	1
RAC1	physical association	0.400	1
ALK	physical association	0.370	1
CNOT1	association	0.350	1
GRK2	association	0.350	1
RPS6KA1	association	0.350	1
STAT3	colocalization	0.270	1

BioGRID (75 interactions; top human partners by supporting records): BNIP2 (Two-hybrid; 3 records), CSK (Affinity Capture-MS; 3 records), EGFR (Two-hybrid; 3 records), PCBP1 (Affinity Capture-MS; 3 records), PTEN (Affinity Capture-MS; 3 records), YAP1 (Affinity Capture-Western; 3 records), RB1 (Reconstituted Complex; 2 records), SF3B4 (Two-hybrid; 2 records), ADRBK1 (Affinity Capture-MS), AMBRA1 (Proximity Label-MS), ARCN1 (Affinity Capture-MS), AURKB (Affinity Capture-MS), BCR (Affinity Capture-MS), BLK (Negative Genetic), CAMK4 (Affinity Capture-MS)

SIGNOR signaling

showing 6 of 8 signaling interactions:

A	Effect	B	Mechanism
regorafenib	“down-regulates activity”	FRK	“chemical inhibition”
FRK	“up-regulates quantity by stabilization”	BRCA1	phosphorylation
FRK	“down-regulates quantity by destabilization”	YAP1	phosphorylation
FRK	“up-regulates quantity by stabilization”	PTEN	phosphorylation
FRK	“up-regulates activity”	PTEN	phosphorylation
FRK	“down-regulates activity”	EGFR	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for FRK: 60 ClinVar records (0 pathogenic / likely pathogenic); 41 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	4
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 1,123):

Position(s)	Effect	Δscore	Sites
6:115942648	acceptor_gain	1.0000
6:115956446	donor_gain	1.0000
6:115956611–115956612	acceptor_loss	1.0000	5
6:115967720–115967721	acceptor_loss	1.0000	6
6:115967727	acceptor_gain	1.0000
6:115968574–115968575	donor_loss	1.0000	3
6:115968740–115968741	acceptor_loss	1.0000	6
6:116003875–116003876	donor_loss	1.0000	4
6:116003999	acceptor_loss	1.0000
6:115942627	acceptor_gain	0.9900

AlphaMissense

1,157 missense substitutions predicted likely pathogenic (of 3,314 scored), across 283 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M342	9	0.970	0.997
M281	9	0.894	0.993
D415	8	0.996	0.998
D354	8	0.995	0.999
N359	8	0.994	0.997
D372	8	0.994	0.999
H352	8	0.993	0.998
F373	8	0.986	0.998
F480	8	0.980	0.998
H164	8	0.945	0.981
H286	8	0.943	0.992
F274	8	0.933	0.989
D60	8	0.927	0.981
N135	8	0.772	0.901
W399	7	0.996	1.000
W417	7	0.996	0.999
K262	7	0.994	1.000
F245	7	0.993	0.999
E425	7	0.987	0.996
W470	7	0.986	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	4.58e-07
Kidney Chromophobe (TCGA)	unfavorable	0.000697
Rectum Adenocarcinoma (TCGA)	favorable	0.000881

Disease associations

OMIM: gene MIM:606573 | disease phenotypes:

GWAS associations

showing 30 of 41 associations:

Study	Trait	p-value
GCST010002_310	Refractive error	2e-36
GCST010241_56	Apolipoprotein A1 levels	2e-19
GCST010204_192	Low density lipoprotein cholesterol levels	1e-18
GCST010245_213	LDL cholesterol levels	4e-17
GCST010242_193	HDL cholesterol levels	6e-17
GCST90013663_82	Alanine aminotransferase levels	5e-16
GCST008079_127	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3e-15
GCST90013664_29	Aspartate aminotransferase levels	5e-15
GCST008078_84	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1e-13
GCST004235_51	Total cholesterol levels	2e-13
GCST008079_157	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5e-13
GCST003678_11	C-reactive protein levels or total cholesterol levels (pleiotropy)	2e-12
GCST010243_59	Apolipoprotein B levels	2e-12
GCST90011898_108	Alanine aminotransferase levels	6e-12
GCST003679_2	C-reactive protein levels or LDL-cholesterol levels (pleiotropy)	8e-12
GCST008078_52	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8e-12
GCST000760_50	Cholesterol, total	2e-10
GCST007614_12	C-reactive protein levels	3e-10
GCST002221_50	Cholesterol, total	1e-9
GCST003992_12	Photic sneeze reflex	2e-9
GCST004233_14	LDL cholesterol levels	2e-9
GCST90011899_146	Aspartate aminotransferase levels	2e-9
GCST90011900_194	Serum alkaline phosphatase levels	2e-9
GCST000759_25	LDL cholesterol	3e-9
GCST008086_103	LDL cholesterol levels in current drinkers	8e-9
GCST011348_7	High density lipoprotein cholesterol levels	8e-9
GCST001100_6	Age-related macular degeneration	1e-8
GCST007094_109	Diastolic blood pressure	2e-8
GCST003075_36	Cognitive decline rate in late mild cognitive impairment	3e-8
GCST007576_79	Chronotype	4e-8

EFO canonical traits (from GWAS)

17 canonical traits:

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004531	urate measurement
EFO:0007710	cognitive decline measurement
EFO:0004458	C-reactive protein measurement
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0004980	appendicular lean mass
EFO:0006336	diastolic blood pressure
EFO:0008328	chronotype measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0007626	emphysema imaging measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004469	HOMA-B
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363074 (PROTEIN FAMILY), CHEMBL4223 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the FRK protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
REGORAFENIB	Small molecule	4

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes FRK — the drug acts on the assembly or class, not necessarily on this subunit alone.

5 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
DASATINIB ANHYDROUS	SRC	10	4
ENMD-981693	SRC	10	2
ILORASERTIB	SRC	10	2
TG100-801	SRC	10	2
XL-228	SRC	10	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 622,377 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 71 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1173655	AFATINIB	4	15,878
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL2105717	CABOZANTINIB	4	11,799
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL2028663	DABRAFENIB	4	13,060
CHEMBL5416410	DASATINIB	4	674
CHEMBL1421	DASATINIB ANHYDROUS	4	55,947
CHEMBL1983268	ENTRECTINIB	4	3,737
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL939	GEFITINIB	4	119,425
CHEMBL1873475	IBRUTINIB	4	8,363
CHEMBL941	IMATINIB	4	113,105
CHEMBL3286830	LORLATINIB	4	3,833
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL255863	NILOTINIB	4	39,362
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL477772	PAZOPANIB	4	16,241
CHEMBL225072	PEMETREXED	4	56,714
CHEMBL1171837	PONATINIB	4
CHEMBL576982	QUIZARTINIB	4
CHEMBL1336	SORAFENIB	4
CHEMBL535	SUNITINIB	4
CHEMBL1289494	TIVOZANIB	4
CHEMBL3348923	TOVORAFENIB	4
CHEMBL24828	VANDETANIB	4
CHEMBL3936761	ZANUBRUTINIB	4
CHEMBL483158	ALISERTIB	3
CHEMBL428690	ALVOCIDIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL1908391	MASITINIB	3
CHEMBL572881	MOTESANIB	3
CHEMBL217092	SARACATINIB	3
CHEMBL101253	VATALANIB	3
CHEMBL206834	BAFETINIB	2
CHEMBL3545396	BMS-690514	2
CHEMBL460702	BMS-777607	2
CHEMBL1967878	CENISERTIB	2
CHEMBL2029988	CEP-32496	2
CHEMBL402548	DANUSERTIB	2
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL3989914	GLESATINIB	2
CHEMBL3039525	GOLVATINIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL564829	MILCICLIB	2
CHEMBL119385	NEFLAMAPIMOD	2
CHEMBL253969	OSI-632	2
CHEMBL607707	PELITINIB	2
CHEMBL3991932	PEXMETINIB	2
CHEMBL475251	R-406	2
CHEMBL558752	RAF-265	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL363648	TAK-715	2

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Src family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
bosutinib	Inhibition	8.66	pIC50
eCF506	Inhibition	8.55	pIC50

Binding affinities (BindingDB)

63 measured of 150 human assays (153 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL3808884	EC50	0.04 nM
3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide	EC50	0.05 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
AP-26113	IC50	0.37 nM
CHEMBL5712062	KI	0.7 nM
Staurosporine	KD	1.7 nM
CHEMBL5088153	IC50	2 nM
CHEMBL5415503	IC50	2.1 nM
CEP-701	KD	3.4 nM
4-[4-[(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	IC50	5.5 nM
Lorlatinib	IC50	5.5 nM	US-11517561: Macrocycle and composition comprising thereof
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	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
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	IC50	5.6 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
Staurosporine, 8	IC50	6.5 nM
Momelotinib	IC50	8 nM	US-9469613: (N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide
CHEMBL4465866	KD	8 nM
CHEMBL4576489	KD	8 nM
ASP-3026	IC50	10 nM
3-(4-amino-7-(piperidin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenol	KD	10 nM
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	IC50	11 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
4-(8-amino-3-{(3R,6S)-6-methyl-1-[(3-methyloxetan-3-yl)carbonyl]piperidin-3-yl}imidazo[1,5-a]pyrazin-1-yl)-3-fluoro-N-[4-(trifluoromethyl)pyridin-2-yl]benzamide	IC50	11 nM
CHEMBL3586447	IC50	11 nM
CHEMBL5404368	IC50	11 nM
CHEMBL4749037	IC50	13 nM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	KI	15 nM	US-10981896: Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase
CHEMBL1240703	KD	15 nM
2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide	IC50	17 nM
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	IC50	19 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
4-(8-amino-3-{(3R)-1-[(3-methyloxetan-3-yl)carbonyl]azepan-3-yl}imidazo[1,5-a]pyrazin-1-yl)-N-[4-(trifluoromethyl)pyridin-2-yl]benzamide	IC50	20 nM
CHEMBL4799627	IC50	20 nM
N-(2,6-difluorophenyl)-5-(3-(2-(5-ethyl-2-methoxy-4-(4-(4-(methylsulfonyl)piperazin-1-yl)piperidin-1-yl)phenylamino)pyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-methoxybenzamide	IC50	27 nM
(R)-4-(8-amino-5-deutero-3-(1-(3-methoxypropanoyl) piperidin-3-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide	IC50	28 nM
CHEMBL4095253	IC50	36 nM
1-(tert-butyl)-3-(4-chlorophenyl)-4-aminopyrazolo[3,4-d]pyrimidine	IC50	36.6 nM	US-10544104: Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases
6-Methyl-biphenyl-3,4’-dicarboxylic acid 3-[(3-tert-butyl-phenyl)-amide] 4’-cyclopropylmethyl-amide	KD	46 nM
(3R,4S)-3-[[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]dithiolan-4-ol	IC50	52 nM	US-10844038: 1,2-dithiolane compounds useful in neuroprotection, autoimmune and cancer diseases and conditions
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	IC50	64 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
CHEMBL4098896	KD	64 nM
CHEMBL4069387	IC50	83 nM
PKC-412	KD	110 nM
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	KD	120 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
CHEMBL4077588	IC50	127 nM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	IC50	175 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
PKC-412	KD	190 nM
CHEMBL4060757	IC50	200 nM
4-{8-amino-3-[(2R)-4-oxetan-3-ylmorpholin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-[4-(trifluoromethyl)pyridin-2-yl]benzamide	IC50	331 nM
CHEMBL4793380	IC50	408 nM
3-[4-(benzylamino)-3-methoxyphenyl]-1-[2-[4-(dimethylamino)piperidin-1-yl]ethyl]pyrazolo[3,4-d]pyrimidin-4-amine	IC50	550 nM	US-10294227: Compounds
CHEMBL1908397	KD	650 nM
CHEMBL4075954	IC50	703 nM

ChEMBL bioactivities

394 potent at pChembl≥5 of 395 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.51	Kd	0.31	nM	DASATINIB
9.00	Kd	1	nM	CHEMBL400402
9.00	Ki	1	nM	CHEMBL1984162
9.00	Ki	1	nM	CHEMBL1993661
8.90	Ki	1.259	nM	CHEMBL1981047
8.89	IC50	1.3	nM	PONATINIB
8.85	Kd	1.4	nM	BOSUTINIB
8.70	Ki	1.995	nM	CHEMBL1992306
8.70	Ki	1.995	nM	ILORASERTIB
8.66	IC50	2.2	nM	BOSUTINIB
8.60	Ki	2.512	nM	TAE-684
8.60	Ki	2.512	nM	CHEMBL1988387
8.60	Ki	2.512	nM	CHEMBL1964692
8.50	Ki	3.162	nM	CHEMBL1970142
8.50	Ki	3.162	nM	CHEMBL1996979
8.50	Ki	3.162	nM	CHEMBL306380
8.50	Ki	3.162	nM	CHEMBL1994938
8.42	Kd	3.8	nM	FORETINIB
8.40	Ki	3.981	nM	CHEMBL1989708
8.40	Ki	3.981	nM	CHEMBL259922
8.39	Kd	4.1	nM	CHEMBL386051
8.34	IC50	4.56	nM	STAUROSPORINE
8.34	Kd	4.571	nM	DASATINIB ANHYDROUS
8.30	Kd	5	nM	DASATINIB
8.30	Kd	5	nM	DASATINIB ANHYDROUS
8.30	Ki	5.012	nM	CHEMBL1998585
8.30	Ki	5.012	nM	CHEMBL2004716
8.30	Ki	5.012	nM	CHEMBL1982466
8.22	Kd	6	nM	CHEMBL450519
8.20	Ki	6.31	nM	CHEMBL1988717
8.20	Ki	6.31	nM	CHEMBL1989708
8.20	Ki	6.31	nM	CHEMBL1090356
8.16	Kd	6.9	nM	CHEMBL5415503
8.10	Ki	7.943	nM	CHEMBL213505
8.00	Ki	10	nM	CHEMBL1974328
8.00	Ki	10	nM	CHEMBL1993424
7.99	IC50	10.3	nM	STAUROSPORINE
7.92	Kd	12	nM	CHEMBL504075
7.90	Ki	12.59	nM	CHEMBL2005886
7.90	Ki	12.59	nM	R-406
7.80	IC50	16	nM	CHEMBL466397
7.80	Ki	15.85	nM	CHEMBL1987034
7.80	Ki	15.85	nM	CHEMBL1977148
7.80	Ki	15.85	nM	CHEMBL2001485
7.80	Ki	15.85	nM	CHEMBL1993243
7.80	Ki	15.85	nM	CHEMBL508928
7.80	Ki	15.85	nM	ENTRECTINIB
7.77	IC50	17	nM	STAUROSPORINE
7.72	IC50	19	nM	CHEMBL4798527
7.70	Ki	19.95	nM	LINIFANIB

PubChem BioAssay actives

169 with measured affinity, of 1501 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	436019: Binding constant for FRK kinase domain	kd	0.0003	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1425007: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0010	uM
Ponatinib	1716397: Binding affinity to human FRK using poly[Glu:Tyr] (4:1) as substrate by radiometric hotspot kinase assay	ic50	0.0013	uM
Bosutinib	624855: Binding constant for FRK kinase domain	kd	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	624855: Binding constant for FRK kinase domain	kd	0.0038	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624855: Binding constant for FRK kinase domain	kd	0.0041	uM
Dasatinib	2148399: Binding affinity to human FRK incubated for 45 mins by Kinobead based pull down assay	kd	0.0046	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	1715339: Inhibition of human FRK using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0046	uM
3-(4-amino-7-piperidin-4-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenol	389097: Binding affinity to human FRK	kd	0.0060	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	1988540: Binding affinity to FRK (unknown origin) assessed as dissociation constant by KINOME scan assay	kd	0.0069	uM
N-[3-[(1S)-1-[(6-chloropyrazin-2-yl)amino]ethyl]phenyl]-3-methylbenzamide	392579: Inhibition of FRK	kd	0.0120	uM
N-(2,6-difluorophenyl)-5-[3-[2-[5-ethyl-2-methoxy-4-[4-(4-methylsulfonylpiperazin-1-yl)piperidin-1-yl]anilino]pyrimidin-4-yl]imidazo[1,2-a]pyridin-2-yl]-2-methoxybenzamide	2167084: Inhibition of N-terminal 6His-tagged recombinant human PTK5 (218 to end residues) expressed in baculovirus infected Sf21 cells by filter binding assay	ic50	0.0160	uM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	1734749: Inhibition of human recombinant PTK5 (218 to end residues) using GGEEEEYFELVKKKK as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis	ic50	0.0190	uM
3-cyano-N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486190: Binding affinity to partial length human FRK expressed in Escherichia coli BL21 by active-site-dependent competition assay	kd	0.0220	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	436019: Binding constant for FRK kinase domain	kd	0.0260	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	624855: Binding constant for FRK kinase domain	kd	0.0270	uM
Ibrutinib	1714864: Inhibition of FRK (unknown origin)	ic50	0.0292	uM
1-[3-tert-butyl-1-(4-chlorophenyl)pyrazol-5-yl]-3-[4-[(6,6-dimethyl-7-oxo-8H-pyrimido[5,4-b][1,4]oxazin-4-yl)amino]-3-methylphenyl]urea	1822458: Inhibition of human PTK5 in presence of ATP by radiometric assay	ic50	0.0320	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	1721752: Inhibition of FRK (unknown origin)	ic50	0.0340	uM
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	1721752: Inhibition of FRK (unknown origin)	ic50	0.0360	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168207: Inhibition of human wild type FRK 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	0.0370	uM
2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine	2161829: Inhibition of human N-terminal GST-fused FRK catalytic domain (223 to 505(end) residues) expressed in baculovirus expression system using Srctide as substrate measured after 1 hr by off-chip mobility shift assay relative to control	ic50	0.0400	uM
4-amino-8-(5-methyl-1H-indazol-6-yl)cinnoline-3-carboxamide	1230685: Inhibition of human recombinant Frk	ic50	0.0410	uM
Pemetrexed	2216457: Inhibition of FRK (unknown origin)	ic50	0.0420	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	1721752: Inhibition of FRK (unknown origin)	ic50	0.0460	uM
1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[4-(6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-ylamino)phenyl]urea	1735635: Inhibition of recombinant human PTK5 (218 to end residues) using GGEEEEYFELVKKKK as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay	ic50	0.0510	uM
Brigatinib	2182821: Inhibition of human FRK using RLGRDKYKTLRQIRQ as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.0520	uM
(16R)-19-amino-13-fluoro-4,8,16-trimethyl-9-oxo-17-oxa-4,5,8,20-tetrazatetracyclo[16.3.1.02,6.010,15]docosa-1(22),2,5,11,13,18,20-heptaene-3-carbonitrile	2187706: Inhibition of GST-tagged recombinant full length FRK (unknown origin) expressed in baculovirus expression system	ic50	0.0530	uM
Lorlatinib	1153118: Inhibition of FRK (unknown origin) by TR-FRET-based Z’-LYTE assay	ic50	0.0530	uM
methyl 5-[[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]methylamino]-1H-pyrrolo[2,3-b]pyridine-2-carboxylate	1301829: Inhibition of GST-tagged full length human recombinant FRK expressed in baculovirus using Fluorescein-Poly GT as substrate	ic50	0.0620	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	624855: Binding constant for FRK kinase domain	kd	0.0680	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	1488582: Inhibition of FRK (unknown origin)	ic50	0.0850	uM
Nilotinib	624855: Binding constant for FRK kinase domain	kd	0.0860	uM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide	624855: Binding constant for FRK kinase domain	kd	0.0870	uM
N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide	436019: Binding constant for FRK kinase domain	kd	0.0990	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	1711658: Inhibition of human FRK	ic50	0.1110	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1425007: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1120	uM
N-(3-tert-butylphenyl)-3-[4-(cyclopropylmethylcarbamoyl)phenyl]-4-methylbenzamide	389097: Binding affinity to human FRK	kd	0.1220	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	1488582: Inhibition of FRK (unknown origin)	ic50	0.1320	uM
Tivozanib	1425007: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1450	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	1488582: Inhibition of FRK (unknown origin)	ic50	0.1510	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	1721752: Inhibition of FRK (unknown origin)	ic50	0.1540	uM
Vandetanib	436019: Binding constant for FRK kinase domain	kd	0.1700	uM
Tovorafenib	1425007: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1720	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	1711658: Inhibition of human FRK	ic50	0.1870	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256598: Average Binding Constant for FRK; NA=Not Active at 10 uM	kd	0.1900	uM
Fedratinib	624855: Binding constant for FRK kinase domain	kd	0.2000	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	1488582: Inhibition of FRK (unknown origin)	ic50	0.2140	uM
5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide	1425007: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2220	uM
1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-methoxyphenyl]-3-[1-(1,3-thiazol-2-yl)ethyl]urea	624855: Binding constant for FRK kinase domain	kd	0.3100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, increases reaction, affects cotreatment, decreases expression	5
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, affects cotreatment	3
afimoxifene	decreases response to substance, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
glycidyl methacrylate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
resorcinol	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ON 01910	increases phosphorylation	1
ponatinib	decreases activity	1
Dasatinib	affects binding	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Caffeine	affects phosphorylation	1
Cycloheximide	decreases expression, decreases reaction	1
Doxorubicin	decreases expression	1
Quercetin	decreases expression	1
Dihydrotestosterone	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1

ChEMBL screening assays

271 unique, capped per target: 269 binding, 1 functional, 1 admet

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*
CHEMBL1964118	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FRK	PubChem BioAssay data set
CHEMBL4414922	ADMET	Inhibition of human FRK using poly[Glu:Tyr] (4:1) as substrate preincubated for 60 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by filter binding method	Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase. — *J Med Chem*

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1MM	Abcam K-562 FRK KO	Cancer cell line	Female
CVCL_D2J7	Abcam Raji FRK KO	Cancer cell line	Male
CVCL_UQ54	Abcam Jurkat FRK KO	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FRK across ~30M SureChEMBL compounds — explore on Sugi Predict.