PTK2

Summary

PTK2 (protein tyrosine kinase 2, HGNC:9611) is a protein-coding gene on chromosome 8q24.3, encoding Focal adhesion kinase 1 (Q05397). Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apopto…. It is a selective cancer dependency (DepMap: 52.5% of cell lines).

This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5747 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 174 total
• Phenotypes (HPO): 2
• Druggable target: yes — 56 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 52.5% of screened cell lines
• MANE Select transcript: NM_001352702

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9611
Approved symbol	PTK2
Name	protein tyrosine kinase 2
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	FAK, FADK, FAK1, PPP1R71
Ensembl gene	ENSG00000169398
Ensembl biotype	protein_coding
OMIM	600758
Entrez	5747

Gene structure

Transcript identifiers

Ensembl transcripts: 80 — 56 protein_coding, 11 protein_coding_CDS_not_defined, 8 nonsense_mediated_decay, 5 retained_intron

ENST00000340930, ENST00000395218, ENST00000430260, ENST00000510126, ENST00000517453, ENST00000517712, ENST00000517887, ENST00000518173, ENST00000518509, ENST00000519024, ENST00000519361, ENST00000519419, ENST00000519465, ENST00000519635, ENST00000519654, ENST00000519881, ENST00000519899, ENST00000519993, ENST00000520045, ENST00000520151, ENST00000520460, ENST00000520475, ENST00000520828, ENST00000520843, ENST00000520892, ENST00000520917, ENST00000521029, ENST00000521059, ENST00000521172, ENST00000521250, ENST00000521332, ENST00000521395, ENST00000521562, ENST00000521791, ENST00000521907, ENST00000521981, ENST00000521985, ENST00000521986, ENST00000522424, ENST00000522684, ENST00000522950, ENST00000523067, ENST00000523388, ENST00000523435, ENST00000523474, ENST00000523539, ENST00000523670, ENST00000523675, ENST00000523679, ENST00000523746, ENST00000523797, ENST00000523803, ENST00000523805, ENST00000524040, ENST00000524202, ENST00000524257, ENST00000524357, ENST00000696786, ENST00000894110, ENST00000894111, ENST00000894112, ENST00000894113, ENST00000894114, ENST00000894115, ENST00000894116, ENST00000894117, ENST00000894118, ENST00000894119, ENST00000934989, ENST00000934990, ENST00000934991, ENST00000943757, ENST00000943758, ENST00000943759, ENST00000943760, ENST00000943761, ENST00000943762, ENST00000943763, ENST00000943764, ENST00000943765

RefSeq mRNA: 130 — MANE Select: NM_001352702 NM_001199649, NM_001316342, NM_001352694, NM_001352695, NM_001352696, NM_001352697, NM_001352698, NM_001352699, NM_001352700, NM_001352701, NM_001352702, NM_001352703, NM_001352704, NM_001352705, NM_001352706, NM_001352707, NM_001352708, NM_001352709, NM_001352710, NM_001352711, NM_001352712, NM_001352713, NM_001352714, NM_001352715, NM_001352716, NM_001352717, NM_001352718, NM_001352719, NM_001352720, NM_001352721, NM_001352722, NM_001352723, NM_001352724, NM_001352725, NM_001352726, NM_001352727, NM_001352728, NM_001352729, NM_001352730, NM_001352731, NM_001352732, NM_001352733, NM_001352734, NM_001352735, NM_001352736, NM_001352737, NM_001352738, NM_001352739, NM_001352740, NM_001352741, NM_001352742, NM_001352743, NM_001352744, NM_001352745, NM_001352746, NM_001352747, NM_001352749, NM_001352750, NM_001352751, NM_001352752, NM_001387584, NM_001387585, NM_001387586, NM_001387587, NM_001387588, NM_001387589, NM_001387590, NM_001387591, NM_001387592, NM_001387603, NM_001387604, NM_001387605, NM_001387606, NM_001387607, NM_001387608, NM_001387609, NM_001387610, NM_001387611, NM_001387612, NM_001387613, NM_001387614, NM_001387615, NM_001387616, NM_001387617, NM_001387618, NM_001387619, NM_001387620, NM_001387621, NM_001387622, NM_001387623, NM_001387624, NM_001387625, NM_001387627, NM_001387628, NM_001387629, NM_001387630, NM_001387631, NM_001387632, NM_001387633, NM_001387634, NM_001387635, NM_001387636, NM_001387637, NM_001387638, NM_001387639, NM_001387640, NM_001387641, NM_001387642, NM_001387643, NM_001387644, NM_001387645, NM_001387646, NM_001387647, NM_001387648, NM_001387649, NM_001387650, NM_001387651, NM_001387652, NM_001387653, NM_001387654, NM_001387655, NM_001387656, NM_001387657, NM_001387658, NM_001387659, NM_001387660, NM_001387661, NM_001387662, NM_005607, NM_153831

CCDS: CCDS56557, CCDS6381, CCDS87628, CCDS94345, CCDS94346, CCDS94347

Canonical transcript exons

ENST00000696786 — 36 exons

Exon	Start	End
ENSE00001351413	140925661	140925749
ENSE00002133514	140657900	140659678
ENSE00003466037	140744652	140744767
ENSE00003468483	140789474	140789526
ENSE00003482075	140702570	140702707
ENSE00003492653	140735251	140735455
ENSE00003497298	140668269	140668424
ENSE00003500566	140764234	140764290
ENSE00003501678	140761165	140761262
ENSE00003502332	140818277	140818354
ENSE00003508343	140830472	140830526
ENSE00003508835	140717598	140717709
ENSE00003516040	140664917	140664997
ENSE00003519376	140803543	140803650
ENSE00003519513	140746760	140746860
ENSE00003531796	140739018	140739107
ENSE00003534716	140864312	140864399
ENSE00003544991	140674298	140674404
ENSE00003553942	140793354	140793384
ENSE00003559533	140700891	140701022
ENSE00003573183	140818880	140819020
ENSE00003592207	140706119	140706205
ENSE00003592818	140752232	140752316
ENSE00003593208	140846260	140846322
ENSE00003605836	140846599	140846678
ENSE00003652180	140686632	140686694
ENSE00003653216	140675460	140675499
ENSE00003659598	140800459	140800576
ENSE00003674907	140743230	140743330
ENSE00003785352	140879471	140879637
ENSE00003798215	140890543	140890769
ENSE00003968348	140762368	140762388
ENSE00003968349	141001125	141001282
ENSE00003968459	140770716	140770799
ENSE00003968460	140669727	140669735
ENSE00003968461	140769575	140769592

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.5666 / max 703.3271, expressed in 1756 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95359	22.5747	1738
95357	6.0391	1537
95360	1.2483	854
95358	1.2360	853
95347	1.0859	93
95349	1.0459	83
95356	0.8000	572
95341	0.6329	249
95351	0.3520	125
95362	0.3446	191

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	98.97	gold quality
colonic epithelium	UBERON:0000397	98.64	gold quality
calcaneal tendon	UBERON:0003701	98.33	gold quality
sural nerve	UBERON:0015488	98.11	gold quality
blood vessel layer	UBERON:0004797	98.03	gold quality
lateral globus pallidus	UBERON:0002476	97.85	gold quality
popliteal artery	UBERON:0002250	97.77	gold quality
tibial artery	UBERON:0007610	97.76	gold quality
adrenal tissue	UBERON:0018303	97.71	gold quality
inferior olivary complex	UBERON:0002127	97.61	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.49	gold quality
right coronary artery	UBERON:0001625	97.27	gold quality
postcentral gyrus	UBERON:0002581	97.27	gold quality
CA1 field of hippocampus	UBERON:0003881	97.16	gold quality
Ammon’s horn	UBERON:0001954	97.10	gold quality
primary visual cortex	UBERON:0002436	97.09	gold quality
subthalamic nucleus	UBERON:0001906	97.07	gold quality
inferior vagus X ganglion	UBERON:0005363	96.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.92	gold quality
parietal lobe	UBERON:0001872	96.88	gold quality
entorhinal cortex	UBERON:0002728	96.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.85	gold quality
aorta	UBERON:0000947	96.79	gold quality
occipital lobe	UBERON:0002021	96.72	gold quality
ventricular zone	UBERON:0003053	96.68	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.64	gold quality
spinal cord	UBERON:0002240	96.61	gold quality
temporal lobe	UBERON:0001871	96.60	gold quality
middle temporal gyrus	UBERON:0002771	96.53	gold quality
buccal mucosa cell	CL:0002336	96.52	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-10596	yes	190.83
E-HCAD-11	yes	23.65
E-CURD-46	yes	9.77
E-MTAB-9801	yes	8.19
E-MTAB-6678	yes	7.98
E-GEOD-99795	no	155.57
E-MTAB-6379	no	30.38
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CUX1, ETV4, FOXC1, GDNF, JUN, KLF8, MYC, MYCN, NANOG, NCOA3, NFKB, PPARD, SMAD1, SMAD2, SP1, TP53, TXK

miRNA regulators (miRDB)

90 targeting PTK2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-370-5P	99.78	66.81	706

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 52.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Tyrosine phosphorylation of FAK regulates localization and downstream signaling with profound effects on cell movement. (PMID:11779709)
• Regulation of G protein-linked guanine nucleotide exchange factors for Rho, PDZ-RhoGEF, and LARG by tyrosine phosphorylation: evidence of a role for focal adhesion kinase (PMID:11799111)
• FAK regulates the activity of Akt/protein kinase B and GSK-3beta and the association of GSK-3beta with FAK to influence insulin-stimulated glycogen synthesis in hepatocytes. (PMID:11809746)
• proliferative effect of fibronectin in combination with T cell lymphokines on psoriatic uninvolved basal keratinocyte progenitors may be due to abnormal in vivo integrin-driven focal adhesion kinase activity and downstream signaling. (PMID:11886520)
• Laminin-10/11 and fibronectin differentially prevent apoptosis induced by serum removal via phosphatidylinositol 3-kinase/Akt- and MEK1/ERK-dependent pathways (Laminin 10; separate entry for Laminin 11). (PMID:11891225)
• comparison with FAK2 of the mechanism of tyrosine phosphorylation upon vWF interaction with glycoprotein Ib-IX-V complex (PMID:11916084)
• Nck-2 interacts with focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase critically involved in the cellular control of motility (PMID:11950595)
• beta1 integrin regulates fibroblast viability through a PI3K/Akt/protein kinase B signaling pathway in response to a matrix-derived mechanical stimulus (PMID:11986332)
• Primary arrest of circulating platelets on collagen involves phosphorylation of Syk, cortactin and focal adhesion kinase (PMID:11988077)
• This study reports two crystal structures of the focal adhesion targeting domain of focal adhesion kinase. (PMID:12005431)
• IGF-I protects the cells from apoptosis by blocking the activation of caspases, which may be responsible for the loss of FAK and Akt. (PMID:12011046)
• REVIEW: The focal adhesion kinase–a regulator of cell migration and invasion (PMID:12049193)
• Mutated focal adhesion kinase induces apoptosis in a human glioma cell line (PMID:12054581)
• The association of focal adhesion kinase with Wiskott-Aldrich syndrome protein is associated with cell migration in stromal cell-derived factor-1alpha-stimulated Jurkat cells (PMID:12135674)
• The results of this study indicate that dual inhibition of focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) signaling pathways can cooperatively enhance apoptosis in breast cancers. (PMID:12167618)
• Cerivastatin-induced inhibition of glioblastoma cell migration was associated with the down-regulation of tyrosine phosphorylation of FAK. FAK phosphorylation correlated well with tumor cell invasiveness. (PMID:12169389)
• Expression of focal adhesion kinase and alpha5 and beta1 integrins in carcinomas and its clinical significance. (PMID:12174366)
• results indicated that the mitochondrial pathway is required for ionizing radiation-induced apoptosis, and focal adhesion kinase overexpression blocks this pathway, rendering antiapoptotic states. (PMID:12215217)
• Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells (PMID:12216109)
• Engagement of CD44 either by its natural ligand hyaluronan or a specific antibody on a cell line induced tyrosine phosphorylation and activation of focal adhesion kinase. (PMID:12297287)
• An altered relationship of FAK and Pyk2 was observed for different tumors and could also be important for osteosarcoma development (PMID:12376862)
• Results reveal a novel mechanism of FAK phosphorylation by signalling cascades involving a member of the LDL receptor family. (PMID:12387730)
• FAK NH(2)-terminal domain fragments have roles independent of Y397, kinase, and FAT domains (PMID:12435390)
• R-Ras promotes focal adhesion formation by signaling to FAK and p130(Cas) through a novel mechanism that differs from but synergizes with the alpha2beta1 integrin. (PMID:12529399)
• TGF-beta1 up-regulates expression of integrins and fibronectin, an effect that is associated with autophosphorylation/activation of FAK. (PMID:12531888)
• Shear-induced platelet aggregation induced by 2B-rVWF binding to platelet GPIb produced pp125FAK at shear rate 4000 s-1 but not at 200 s-1 (PMID:12543870)
• caspase-3-mediated proteolysis of FAK, an anti-apoptotic protein, is regulated by hsp72 (PMID:12611892)
• FAK and Pyk2 function as important signaling effectors in gliomas and indicate that their differential regulation may be determining factors in the temporal development of proliferative or migrational phenotypes. (PMID:12651906)
• This review of recent studeis provides considerable insight into the functional roles and signaling mechanisms of FAK as a positive regulator of both cell motility and cell survival. (PMID:12700132)
• Augmented activation of FAK is an immediate signaling event required for the trans-regulation of integrin alpha L beta 2 by alpha 4 beta 1 in Jurkat T cells. (PMID:12794117)
• Decidual beta1 integrin and FAK participate in this final step of implantation. (PMID:12803239)
• FAK activity is regulated by low molecular weight phosphotyrosine phosphatase in human cells (PMID:12815062)
• FAK is activated by VEGF in human brain microvascular endothelial cells (PMID:12844492)
• Inhibition of FAK by antisense oligonucleotideds enhances the sensitivity of breast cancer cells to campothecin. (PMID:12847914)
• CIB regulates platelet spreading through the regulation of FAK activation. (PMID:12881299)
• FAK has a role in the pathology of human cancer [review] (PMID:12884911)
• TIMP-1 activates cell survival signaling pathways involving focal adhesion kinase, phosphatidylinositol 3-kinase, and ERKs in human breast epithelial cells (PMID:12904305)
• both c-Src/PI3K and c-Src/Fak/Erk1/2 pathways are involved in the up-regulation of c-myc and cyclin d1 expression mediated by prolactin (PMID:12907754)
• FAK and Src are important survival factors, playing a role in protecting colon cancer cell lines from Adenovirus-containing FAK-CD (Ad-FAK-CD)-induced apoptosis (PMID:12939401)
• beta1 integrin/FAK-mediated signaling on osteoblasts could be involved in ICAM-1- and RANKL-dependent osteoclast maturation (PMID:12954625)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptk2ab	ENSDARG00000004672
danio_rerio	ptk2aa	ENSDARG00000100456
mus_musculus	Ptk2	ENSMUSG00000022607
rattus_norvegicus	Ptk2	ENSRNOG00000007916

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), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Focal adhesion kinase 1 — Q05397 (reviewed: Q05397)

Alternative names: Focal adhesion kinase-related nonkinase, Protein phosphatase 1 regulatory subunit 71, Protein-tyrosine kinase 2, p125FAK, pp125FAK

All UniProt accessions (34): A0A1D5RMT1, A0A8Q3WLM4, B4DWJ1, E5RFW9, E5RG54, E5RG66, E5RG80, E5RG86, E5RGA6, E5RGP1, E5RH01, E5RH08, E5RH48, E5RHD8, E5RHK7, E5RI03, E5RI29, Q05397, E5RI72, E5RII9, E5RIK4, E5RIR5, E5RJI4, E5RJN1, E5RJP0, E5RJQ2, E7ESA6, E9PEI4, H0YAS0, H0YB16, H0YB33, H0YB99, H0YBP1, H0YBZ1

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.

Subunit / interactions. Interacts (via first Pro-rich region) with CAS family members (via SH3 domain), including BCAR1, BCAR3, and CASS4. Interacts with NEDD9 (via SH3 domain). Interacts with GIT1. Interacts with SORBS1. Interacts with ARHGEF28. Interacts with SHB. Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL. Interacts with PXN and TLN1. Interacts with STAT1. Interacts with DCC. Interacts with WASL. Interacts with ARHGEF7. Interacts with GRB2 and GRB7. Component of a complex that contains at least FER, CTTN and PTK2/FAK1. Interacts with BMX. Interacts with TGFB1I1. Interacts with STEAP4. Interacts with ZFYVE21. Interacts with ESR1. Interacts with PIK3R1 or PIK3R2. Interacts with SRC, FGR, FLT4 and RET. Interacts with EPHA2 in resting cells; activation of EPHA2 recruits PTPN11, leading to dephosphorylation of PTK2/FAK1 and dissociation of the complex. Interacts with EPHA1 (kinase activity-dependent). Interacts with CD4; this interaction requires the presence of HIV-1 gp120. Interacts with PIAS1. Interacts with ARHGAP26 and SHC1. Interacts with RB1CC1; this inhibits PTK2/FAK1 activity and activation of downstream signaling pathways. Interacts with P53/TP53 and MDM2. Interacts with LPXN (via LD motif 3). Interacts with MISP. Interacts with CIB1 isoform 2. Interacts with CD36. Interacts with EMP2; regulates PTK2 activation and localization. Interacts with DSCAM. Interacts with AMBRA1. Interacts (when tyrosine-phosphorylated) with tensin TNS1; the interaction is increased by phosphorylation of TNS1.

Subcellular location. Cell junction. Focal adhesion. Cell membrane. Cytoplasm. Perinuclear region. Cell cortex. Cytoskeleton. Microtubule organizing center. Centrosome. Nucleus. Cilium basal body.

Tissue specificity. Detected in B and T-lymphocytes. Isoform 1 and isoform 6 are detected in lung fibroblasts (at protein level). Ubiquitous. Expressed in epithelial cells (at protein level).

Post-translational modifications. Phosphorylated on tyrosine residues upon activation, e.g. upon integrin signaling. Tyr-397 is the major autophosphorylation site, but other kinases can also phosphorylate this residue. Phosphorylation at Tyr-397 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-576, Tyr-577 and at additional tyrosine residues. FGR promotes phosphorylation at Tyr-397 and Tyr-576. FER promotes phosphorylation at Tyr-577, Tyr-861 and Tyr-925, even when cells are not adherent. Tyr-397, Tyr-576 and Ser-722 are phosphorylated only when cells are adherent. Phosphorylation at Tyr-397 is important for interaction with BMX, PIK3R1 and SHC1. Phosphorylation at Tyr-925 is important for interaction with GRB2. Dephosphorylated by PTPN11; PTPN11 is recruited to PTK2 via EPHA2 (tyrosine phosphorylated). Microtubule-induced dephosphorylation at Tyr-397 is crucial for the induction of focal adhesion disassembly; this dephosphorylation could be catalyzed by PTPN11 and regulated by ZFYVE21. Phosphorylation on tyrosine residues is enhanced by NTN1. Sumoylated; this enhances autophosphorylation.

Disease relevance. Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.

Activity regulation. Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop. Phosphorylation at Tyr-576 and Tyr-577 is required for maximal kinase activity. Inhibited by TAC544, TAE226, PF-573,228 and PF-562,271.

Domain organisation. The Pro-rich regions interact with the SH3 domain of CAS family members, such as BCAR1 and NEDD9, and with the GTPase activating protein ARHGAP26. The focal AT domain mediates the localization of FAK1 to focal adhesions.

Miscellaneous. Produced by alternative promoter usage.

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

Isoforms (7)

UniProt ID	Names	Canonical?
Q05397-1	1	yes
Q05397-2	2
Q05397-3	3
Q05397-4	4
Q05397-5	5
Q05397-6	6, FRNK
Q05397-7	7

RefSeq proteins (130): NP_001186578, NP_001303271, NP_001339623, NP_001339624, NP_001339625, NP_001339626, NP_001339627, NP_001339628, NP_001339629, NP_001339630, NP_001339631, NP_001339632, NP_001339633, NP_001339634, NP_001339635, NP_001339636, NP_001339637, NP_001339638, NP_001339639, NP_001339640, NP_001339641, NP_001339642, NP_001339643, NP_001339644, NP_001339645, NP_001339646, NP_001339647, NP_001339648, NP_001339649, NP_001339650, NP_001339651, NP_001339652, NP_001339653, NP_001339654, NP_001339655, NP_001339656, NP_001339657, NP_001339658, NP_001339659, NP_001339660, NP_001339661, NP_001339662, NP_001339663, NP_001339664, NP_001339665, NP_001339666, NP_001339667, NP_001339668, NP_001339669, NP_001339670, NP_001339671, NP_001339672, NP_001339673, NP_001339674, NP_001339675, NP_001339676, NP_001339678, NP_001339679, NP_001339680, NP_001339681, NP_001374513, NP_001374514, NP_001374515, NP_001374516, NP_001374517, NP_001374518, NP_001374519, NP_001374520, NP_001374521, NP_001374532, NP_001374533, NP_001374534, NP_001374535, NP_001374536, NP_001374537, NP_001374538, NP_001374539, NP_001374540, NP_001374541, NP_001374542, NP_001374543, NP_001374544, NP_001374545, NP_001374546, NP_001374547, NP_001374548, NP_001374549, NP_001374550, NP_001374551, NP_001374552, NP_001374553, NP_001374554, NP_001374556, NP_001374557, NP_001374558, NP_001374559, NP_001374560, NP_001374561, NP_001374562, NP_001374563, NP_001374564, NP_001374565, NP_001374566, NP_001374567, NP_001374568, NP_001374569, NP_001374570, NP_001374571, NP_001374572, NP_001374573, NP_001374574, NP_001374575, NP_001374576, NP_001374577, NP_001374578, NP_001374579, NP_001374580, NP_001374581, NP_001374582, NP_001374583, NP_001374584, NP_001374585, NP_001374586, NP_001374587, NP_001374588, NP_001374589, NP_001374590, NP_001374591, NP_005598, NP_722560 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR005189	Focal_adhesion_kin_target_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR020635	Tyr_kinase_cat_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035963	FERM_2	Homologous_superfamily
IPR036137	Focal_adhe_kin_target_dom_sf	Homologous_superfamily
IPR041390	FADK_N	Domain
IPR041784	FAK1/PYK2_FERM_C	Domain
IPR049385	FAK1-like_FERM_C	Domain

Pfam: PF00373, PF03623, PF07714, PF18038, PF21477

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 (137 total): helix 40, strand 26, modified residue 19, splice variant 12, turn 10, region of interest 5, sequence variant 5, compositionally biased region 4, binding site 3, domain 3, mutagenesis site 3, sequence conflict 3, initiator methionine 1, chain 1, active site 1, cross-link 1

Structure

Experimental structures (PDB)

40 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6YOJ	X-RAY DIFFRACTION	1.36
6YT6	X-RAY DIFFRACTION	1.54
4I4E	X-RAY DIFFRACTION	1.55
1MP8	X-RAY DIFFRACTION	1.6
4EBV	X-RAY DIFFRACTION	1.67
4I4F	X-RAY DIFFRACTION	1.75
6YQ1	X-RAY DIFFRACTION	1.78
3PXK	X-RAY DIFFRACTION	1.79
6YVS	X-RAY DIFFRACTION	1.81
6YVY	X-RAY DIFFRACTION	1.92
6YR9	X-RAY DIFFRACTION	1.93
7W8I	X-RAY DIFFRACTION	1.94
1K04	X-RAY DIFFRACTION	1.95
4GU6	X-RAY DIFFRACTION	1.95
6PW8	X-RAY DIFFRACTION	1.95
6I8Z	X-RAY DIFFRACTION	1.99
4K9Y	X-RAY DIFFRACTION	2
6LES	X-RAY DIFFRACTION	2
4Q9S	X-RAY DIFFRACTION	2.07
7W8B	X-RAY DIFFRACTION	2.09
7W7Z	X-RAY DIFFRACTION	2.15
7W9U	X-RAY DIFFRACTION	2.16
2IJM	X-RAY DIFFRACTION	2.19
3BZ3	X-RAY DIFFRACTION	2.2
7PI4	X-RAY DIFFRACTION	2.24
6YXV	X-RAY DIFFRACTION	2.3
2ETM	X-RAY DIFFRACTION	2.3
1OW6	X-RAY DIFFRACTION	2.35
4KAO	X-RAY DIFFRACTION	2.39
4GU9	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05397-F1	75.10	0.46

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): 546 (proton acceptor)

Ligand- & substrate-binding residues (3): 428–434; 454; 500–502

Post-translational modifications (20): 2, 5, 13, 29, 54, 397, 407, 570, 576, 577, 580, 722, 732, 843, 861, 887, 910, 914, 925, 152

Mutagenesis-validated functional residues (3):

Position	Phenotype
397	abolishes autophosphorylation. abolishes interaction with src and activation of bmx. reduces phosphorylation of nedd9.
928	loss of interaction with tgfb1i1.
1034	loss of interaction with tgfb1i1.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-111465	Apoptotic cleavage of cellular proteins
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-354192	Integrin signaling
R-HSA-354194	GRB2:SOS provides linkage to MAPK signaling for Integrins
R-HSA-372708	p130Cas linkage to MAPK signaling for integrins
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-391160	Signal regulatory protein family interactions
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-418885	DCC mediated attractive signaling
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-8874081	MET activates PTK2 signaling
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells

MSigDB gene sets: 0 (showing top):

GO Biological Process (54): angiogenesis (GO:0001525), placenta development (GO:0001890), heart morphogenesis (GO:0003007), signal complex assembly (GO:0007172), epidermal growth factor receptor signaling pathway (GO:0007173), transforming growth factor beta receptor signaling pathway (GO:0007179), integrin-mediated signaling pathway (GO:0007229), axon guidance (GO:0007411), positive regulation of cell population proliferation (GO:0008284), regulation of cell shape (GO:0008360), regulation of endothelial cell migration (GO:0010594), regulation of epithelial cell migration (GO:0010632), positive regulation of epithelial cell migration (GO:0010634), positive regulation of epithelial to mesenchymal transition (GO:0010718), positive regulation of macrophage chemotaxis (GO:0010759), positive regulation of fibroblast migration (GO:0010763), cell migration (GO:0016477), negative regulation of cell-cell adhesion (GO:0022408), establishment of cell polarity (GO:0030010), regulation of cell adhesion (GO:0030155), positive regulation of cell migration (GO:0030335), negative regulation of cell adhesion mediated by integrin (GO:0033629), positive regulation of cell-cell adhesion mediated by integrin (GO:0033634), detection of muscle stretch (GO:0035995), netrin-activated signaling pathway (GO:0038007), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), regulation of cell population proliferation (GO:0042127), negative regulation of apoptotic process (GO:0043066), regulation of osteoblast differentiation (GO:0045667), vascular endothelial growth factor receptor signaling pathway (GO:0048010), ephrin receptor signaling pathway (GO:0048013), cell motility (GO:0048870), regulation of cytoskeleton organization (GO:0051493), regulation of focal adhesion assembly (GO:0051893), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), growth hormone receptor signaling pathway (GO:0060396), positive regulation of wound healing (GO:0090303), vascular endothelial cell response to oscillatory fluid shear stress (GO:0097706), positive regulation of macrophage proliferation (GO:0120041), regulation of substrate adhesion-dependent cell spreading (GO:1900024)

GO Molecular Function (16): actin binding (GO:0003779), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), protein tyrosine phosphatase activity (GO:0004725), integrin binding (GO:0005178), ATP binding (GO:0005524), JUN kinase binding (GO:0008432), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), SH2 domain binding (GO:0042169), molecular function activator activity (GO:0140677), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (16): stress fiber (GO:0001725), nucleus (GO:0005634), centrosome (GO:0005813), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cilium (GO:0005929), cell cortex (GO:0005938), ciliary basal body (GO:0036064), perinuclear region of cytoplasm (GO:0048471), ciliary tip (GO:0097542), cytoplasm (GO:0005737), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Integrin signaling	2
Apoptotic execution phase	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Signal Transduction	1
Platelet Aggregation (Plug Formation)	1
Axon guidance	1
Cell-Cell communication	1
EPH-Ephrin signaling	1
Netrin-1 signaling	1
Signaling by VEGF	1
RHO GTPase Effectors	1
MAPK1/MAPK3 signaling	1
MET promotes cell motility	1
ESR-mediated signaling	1
Extra-nuclear estrogen signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	3
regulation of cell migration	2
epithelial cell migration	2
positive regulation of cell migration	2
microtubule organizing center	2
cell periphery	2
cilium	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
animal organ development	1
heart development	1
animal organ morphogenesis	1
regulation of signal transduction	1
protein-containing complex assembly	1
ERBB signaling pathway	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell surface receptor signaling pathway	1
axonogenesis	1
neuron projection guidance	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of cell morphogenesis	1
regulation of biological quality	1
endothelial cell migration	1
regulation of multicellular organismal process	1
regulation of epithelial cell migration	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
fibroblast migration	1
regulation of fibroblast migration	1

Protein interactions and networks

STRING

3604 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTK2	PXN	P49023	999
PTK2	VCL	P18206	998
PTK2	TLN1	Q9Y490	997
PTK2	BCAR1	P56945	997
PTK2	TLN2	Q9Y4G6	997
PTK2	RB1CC1	Q8TDY2	993
PTK2	FOXO3	O43524	992
PTK2	SRC	P12931	988
PTK2	GRB2	P29354	984
PTK2	FYN	P06241	956
PTK2	SHC1	P29353	947
PTK2	ZYX	Q15942	934
PTK2	ITGB1	P05556	929
PTK2	EGFR	P00533	926
PTK2	CRK	P46108	899

IntAct

232 interactions, top by confidence:

A	B	Type	Score
PTK2	PXN	psi-mi:“MI:0915”(physical association)	0.940
PXN	PTK2	psi-mi:“MI:0915”(physical association)	0.940
PXN	PTK2	psi-mi:“MI:0403”(colocalization)	0.940
PTK2	SRC	psi-mi:“MI:0915”(physical association)	0.920
SRC	PTK2	psi-mi:“MI:0915”(physical association)	0.920
PTK2	SRC	psi-mi:“MI:2364”(proximity)	0.920
CDK5	FIBP	psi-mi:“MI:0914”(association)	0.840
PTK2	TP53	psi-mi:“MI:0407”(direct interaction)	0.750
TP53	PTK2	psi-mi:“MI:0915”(physical association)	0.750
PTK2	TP53	psi-mi:“MI:0915”(physical association)	0.750
TP53	PTK2	psi-mi:“MI:0407”(direct interaction)	0.750

BioGRID (506): YES1 (Two-hybrid), SOCS3 (Two-hybrid), DEF6 (Two-hybrid), PTK2 (Two-hybrid), SOCS2 (Two-hybrid), ATG12 (Two-hybrid), PTK2 (Co-fractionation), TRMT6 (Co-fractionation), PTK2 (Affinity Capture-MS), PTK2 (Reconstituted Complex), PTK2 (Two-hybrid), PTK2 (Two-hybrid), PTK2 (Two-hybrid), PTK2 (Two-hybrid), PTK2 (Two-hybrid)

ESM2 similar proteins: A0A3Q1LSX9, A1A5G0, A1A5K2, A2A5R2, A2APV2, A2VE70, D3ZYR1, O00203, O04376, O35643, O60308, O75122, P52303, Q05397, Q08AM6, Q08DS7, Q0JRZ9, Q10567, Q13367, Q28FH2, Q32PG1, Q3UQN2, Q4U0G1, Q561M0, Q5R807, Q5ZIW5, Q6NUP7, Q6NXC0, Q6NYW6, Q6ZPF4, Q7TSU1, Q7YRF1, Q7Z460, Q80TV8, Q8BRT1, Q8C0Y0, Q8IVF7, Q8LF36, Q8N7B6, Q8RW96

Diamond homologs: A0A2R6XIK6, A2VDU3, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, F4JTP5, G5EE56, O01700, O22558, O35346, O43283, O43318, O64768, P08630, P0C8E4, P0CD62, P18106, P18160, P18161, P29317, P32577, P34152, P41239, P41240, P41241, P42680, P42686, P42690, P51813, P80192, P97504, Q00944, Q02779, Q02977, Q03145, Q05397, Q05609, Q0VBZ0

SIGNOR signaling

150 interactions.

A	Effect	B	Mechanism
PTPN12	down-regulates	PTK2	dephosphorylation
PTK2	up-regulates	PTK2	phosphorylation
SRC	up-regulates	PTK2	phosphorylation
CAMK2A	up-regulates	PTK2	phosphorylation
PTK2	unknown	SH3GL1	phosphorylation
PTPN1	down-regulates	PTK2	dephosphorylation
PTK2B	up-regulates	PTK2	phosphorylation
MET	up-regulates	PTK2	phosphorylation
PTPN11	down-regulates	PTK2	dephosphorylation
EGFR	up-regulates	PTK2	phosphorylation
PDGFRB	up-regulates	PTK2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	9	44.1×	3e-11
Regulation of signaling by CBL	9	42.2×	4e-11
Downstream signal transduction	11	39.5×	5e-13
Signaling by CSF3 (G-CSF)	7	37.7×	3e-08
Regulation of KIT signaling	6	34.0×	9e-07
DCC mediated attractive signaling	5	33.7×	1e-05
Signaling by CSF1 (M-CSF) in myeloid cells	10	32.6×	4e-11
Signaling by SCF-KIT	13	30.4×	1e-13

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	6	34.5×	4e-06
positive regulation of Rac protein signal transduction	6	31.9×	5e-06
negative regulation of inflammatory response to antigenic stimulus	6	29.6×	7e-06
peptidyl-tyrosine phosphorylation	7	24.2×	4e-06
ephrin receptor signaling pathway	8	22.6×	7e-07
epidermal growth factor receptor signaling pathway	10	20.3×	4e-08
T cell costimulation	6	18.4×	8e-05
substrate adhesion-dependent cell spreading	6	16.9×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	11
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

7270 predictions. Top by Δscore:

Variant	Effect	Δscore
8:140659674:TCAAT:T	acceptor_gain	1.0000
8:140659675:CAAT:C	acceptor_gain	1.0000
8:140659675:CAATC:C	acceptor_gain	1.0000
8:140659676:AATC:A	acceptor_loss	1.0000
8:140659677:ATCT:A	acceptor_loss	1.0000
8:140659678:TC:T	acceptor_loss	1.0000
8:140659679:C:CC	acceptor_gain	1.0000
8:140659680:T:G	acceptor_loss	1.0000
8:140668286:A:AC	donor_gain	1.0000
8:140668286:ACT:A	donor_gain	1.0000
8:140668287:C:CC	donor_gain	1.0000
8:140668287:CTC:C	donor_gain	1.0000
8:140674293:CCCA:C	donor_loss	1.0000
8:140674294:CCA:C	donor_loss	1.0000
8:140674295:CA:C	donor_loss	1.0000
8:140674296:A:C	donor_loss	1.0000
8:140674297:CC:C	donor_loss	1.0000
8:140674299:TTGAC:T	donor_gain	1.0000
8:140674402:GATC:G	acceptor_loss	1.0000
8:140674403:ATC:A	acceptor_loss	1.0000
8:140674404:TCT:T	acceptor_loss	1.0000
8:140674405:C:A	acceptor_loss	1.0000
8:140674405:C:CC	acceptor_gain	1.0000
8:140674406:T:G	acceptor_loss	1.0000
8:140700886:ATTAC:A	donor_loss	1.0000
8:140700887:TTA:T	donor_loss	1.0000
8:140700888:TA:T	donor_loss	1.0000
8:140700889:A:AC	donor_gain	1.0000
8:140700890:C:CC	donor_gain	1.0000
8:140700890:C:G	donor_loss	1.0000

AlphaMissense

7236 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:140659521:A:G	L1035P	1.000
8:140659529:T:A	K1032N	1.000
8:140659529:T:G	K1032N	1.000
8:140659530:T:A	K1032I	1.000
8:140659533:G:T	A1031D	1.000
8:140659534:C:G	A1031P	1.000
8:140659542:G:T	A1028D	1.000
8:140659545:A:G	L1027P	1.000
8:140659554:G:T	A1024D	1.000
8:140659635:A:G	L997P	1.000
8:140664981:A:G	L961P	1.000
8:140668330:A:T	V935D	1.000
8:140668342:A:G	L931P	1.000
8:140706197:T:A	R717S	1.000
8:140706197:T:G	R717S	1.000
8:140706198:C:G	R717T	1.000
8:140735254:A:G	L676P	1.000
8:140735266:A:G	L672P	1.000
8:140735304:C:A	W659C	1.000
8:140735304:C:G	W659C	1.000
8:140735305:C:G	W659S	1.000
8:140735306:A:G	W659R	1.000
8:140735306:A:T	W659R	1.000
8:140735307:G:C	C658W	1.000
8:140735309:A:G	C658R	1.000
8:140735320:A:G	L654P	1.000
8:140735327:A:C	Y652D	1.000
8:140735329:A:G	L651P	1.000
8:140735340:A:C	C647W	1.000
8:140735341:C:T	C647Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000004403 (8:140751778 T>A), RS1000005223 (8:140850110 C>T), RS1000006469 (8:140918684 C>A), RS1000009418 (8:140755802 A>G), RS1000031456 (8:140971022 T>G), RS1000048474 (8:140679430 G>A,C), RS1000050271 (8:140766101 C>A), RS1000051061 (8:140761797 A>G), RS1000052945 (8:140811613 G>T), RS1000058866 (8:140745004 G>A), RS1000061651 (8:140701534 T>C), RS1000070046 (8:140837225 G>A,C), RS1000084359 (8:140803869 T>C), RS1000091365 (8:140682647 A>C), RS1000096480 (8:140858963 T>C)

Disease associations

OMIM: gene MIM:600758 | disease phenotypes: MIM:209850, MIM:176700

GenCC curated gene-disease

Mondo (3): enophthalmos (MONDO:0001210), autism (MONDO:0005260), autosomal dominant prognathism (MONDO:0008312)

Orphanet (1): Autosomal dominant prognathism (Orphanet:2964)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000490	Deeply set eye
HP:0000717	Autism

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST001043_2	Response to interferon beta therapy	3.000000e-08
GCST002928_24	Nickel levels	5.000000e-06
GCST003941_17	Acute graft versus host disease in bone marrow transplantation (recipient effect)	4.000000e-07
GCST004630_275	Mean corpuscular hemoglobin	2.000000e-09
GCST006061_24	Atrial fibrillation	2.000000e-10
GCST006061_43	Atrial fibrillation	1.000000e-09
GCST006414_132	Atrial fibrillation	1.000000e-09
GCST006630_16	Diastolic blood pressure	1.000000e-15
GCST007327_142	Smoking status (ever vs never smokers)	4.000000e-09
GCST008357_14	Mood instability	8.000000e-12
GCST010243_65	Apolipoprotein B levels	3.000000e-08
GCST010245_86	LDL cholesterol levels	1.000000e-08
GCST010320_86	PR interval	3.000000e-09
GCST010321_14	PR interval	1.000000e-09
GCST010727_21	Deep white matter hyperintensities	1.000000e-06
GCST012332_20	Multisite chronic pain	3.000000e-08
GCST90000025_458	Appendicular lean mass	2.000000e-17
GCST90002404_103	Red cell distribution width	5.000000e-10

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004599	acute graft vs. host disease
EFO:0004527	mean corpuscular hemoglobin
EFO:0006336	diastolic blood pressure
EFO:0004318	smoking behavior
EFO:0008475	mood instability measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004462	PR interval
EFO:0005665	white matter hyperintensity measurement
EFO:0010100	multisite chronic pain
EFO:0004980	appendicular lean mass
EFO:0009188	Red cell distribution width

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D015841	Enophthalmos	C11.675.319
D008313	Malocclusion, Angle Class III	C07.793.494.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2695 (SINGLE PROTEIN), CHEMBL3301389 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523741 (PROTEIN-PROTEIN INTERACTION), CHEMBL4680052 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

56 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 362,451 (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
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2103830	FOSTAMATINIB	4	3,841
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3286830	LORLATINIB	4	3,598
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL4298138	REPOTRECTINIB	4	1,038
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL1233528	VOLASERTIB	3	1,511
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL3545308	ROCILETINIB	3	1,729
CHEMBL483158	ALISERTIB	3	2,305
CHEMBL50	QUERCETIN	3	74,559
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL1231124	AZD-1480	2
CHEMBL1721885	SU-014813	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1976040	ADAVOSERTIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL3657311	IFEBEMTINIB	2
CHEMBL3689071	NARMAFOTINIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Fak family

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
narmafotinib	Inhibition	9.68	pKd
VS-4718	Inhibition	8.82	pIC50
PF-562271	Inhibition	8.82	pIC50
CEP-37440	Inhibition	8.7	pIC50
NVP-TAE 226	Inhibition	8.26	pIC50
YHJ1039	Inhibition	8.15	pIC50
conteltinib	Inhibition	7.7	pIC50
ENMD-2076	Inhibition	7.26	pIC50
compound 30 [PMID: 23414845]	Inhibition	6.19	pIC50

Binding affinities (BindingDB)

918 measured of 1367 human assays (1376 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[2-[2-[2-[(2-methyl-3,4-dihydro-1H-isoquinolin-6-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]acetamide	IC50	0.3 nM	US-9012461: FAK inhibitors
2-[2-[2-[2-[4-(1-acetylpiperidin-4-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]acetamide	IC50	0.39 nM	US-9012461: FAK inhibitors
US20250214967, Compound A6	IC50	0.39 nM	US-20250214967: FAK DEGRADERS, PHARMACEUTICAL COMPOSITIONS, AND THERAPEUTIC APPLICATIONS
N-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-4-((4-(((3-(N-methylmethylsulfonamido)pyrazin-2-yl)methyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzamide	IC50	0.4 nM	US-20250214967: FAK DEGRADERS, PHARMACEUTICAL COMPOSITIONS, AND THERAPEUTIC APPLICATIONS
US20250214967, Compound A7	IC50	0.47 nM	US-20250214967: FAK DEGRADERS, PHARMACEUTICAL COMPOSITIONS, AND THERAPEUTIC APPLICATIONS
2-[2-[2-[2-[4-(4-acetylpiperazin-1-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]acetamide	IC50	0.6 nM	US-9012461: FAK inhibitors
2-[2-[2-[2-[4-(4-acetylpiperidin-1-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]acetamide	IC50	0.77 nM	US-9012461: FAK inhibitors
2-[2-[2-[2-[4-(4-aminopiperidin-1-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]acetamide	IC50	0.81 nM	US-9012461: FAK inhibitors
N-((4-acrylamidocyclohexyl)methyl)-3-methoxy-4-((4-(((3-(N-methylmethanesulfonylamido)pyrazin-2-yl)methyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzamide	IC50	0.9 nM	US-20250127800: PYRIMIDINE OR PYRIDINE DERIVATIVE AND MEDICINAL USE THEREOF
(R) 2-((2-((4-(((3-(1-acryloylpiperidin-3-yl)phenyl)amino)methyl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)-N-methoxybenzamide	IC50	0.97 nM	US-20250127800: PYRIMIDINE OR PYRIDINE DERIVATIVE AND MEDICINAL USE THEREOF
2-chloro-4-[[5-chloro-4-[(1,2-dimethyl-3-oxo-1,2-dihydroinden-4-yl)oxy]pyrimidin-2-yl]amino]-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-5-methoxybenzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
3-methoxy-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-(1-methylpiperidin-4-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-chloro-4-[[5-chloro-4-[[(1S)-1,2-dimethyl-3-oxo-1H-isoindol-4-yl]oxy]pyrimidin-2-yl]amino]-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-5-methoxybenzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
N-[(3S,4R)-3-fluoro-1-methylpiperidin-4-yl]-3-methoxy-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-fluoro-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-5-methoxy-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-chloro-5-methoxy-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-(1-methylpiperidin-4-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-fluoro-5-methoxy-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-(1-methylpiperidin-4-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-3-methoxy-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
4-[[5-chloro-4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]pyrimidin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
4-[[5-chloro-4-[(2-methoxy-3-oxo-1H-isoindol-4-yl)oxy]pyrimidin-2-yl]amino]-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
4-[[4-[(1,2-dimethyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-3-methoxybenzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
7-[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxy-2,3-dimethyl-3H-isoindol-1-one	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-chloro-4-[[5-chloro-4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]pyrimidin-2-yl]amino]-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
7-[2-[4-[(dimethylamino)methyl]-2-methoxyanilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxy-2-methyl-3H-isoindol-1-one	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
7-[2-[2-methoxy-4-(pyrrolidin-1-ylmethyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxy-2-methyl-3H-isoindol-1-one	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
7-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxy-2-methyl-3H-isoindol-1-one	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
4-[[4-[(1,2-dimethyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
7-[2-[4-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-2-methoxyanilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxy-2,3-dimethyl-3H-isoindol-1-one	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-chloro-4-[[4-[(1,2-dimethyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-4-[(3-oxo-1,2-dihydroinden-4-yl)oxy]pyrimidine-5-carbonitrile	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-chloro-4-[[5-cyano-4-[(3-oxo-1,2-dihydroinden-4-yl)oxy]pyrimidin-2-yl]amino]-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-fluoro-5-methoxy-4-[[4-[(2-methoxy-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-(1-methylpiperidin-4-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-fluoro-5-methoxy-4-[[4-[(2-methoxy-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-[(3R)-1-methylpiperidin-3-yl]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
3-methoxy-4-[[4-[(2-methoxy-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-[(3R)-1-methylpiperidin-3-yl]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)-4-[[5-(trifluoromethyl)-4-(1,1,2-trimethyl-3-oxoisoindol-4-yl)oxypyrimidin-2-yl]amino]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-fluoro-5-methoxy-N-[(3S,4R)-3-methoxy-1-methylpiperidin-4-yl]-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-chloro-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-5-methoxy-4-[[5-(trifluoromethyl)-4-(1,1,2-trimethyl-3-oxoisoindol-4-yl)oxypyrimidin-2-yl]amino]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-chloro-5-methoxy-N-[(3S,4R)-3-methoxy-1-methylpiperidin-4-yl]-4-[[5-(trifluoromethyl)-4-(1,1,2-trimethyl-3-oxoisoindol-4-yl)oxypyrimidin-2-yl]amino]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
N-[2-(dimethylamino)ethyl]-2-fluoro-5-methoxy-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
N-[(2S)-2,3-dihydroxypropyl]-2-fluoro-5-methoxy-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-chloro-5-methoxy-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-[(3S)-1-methylpiperidin-3-yl]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-chloro-4-[[5-chloro-4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]pyrimidin-2-yl]amino]-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-5-methoxybenzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-chloro-4-[[5-chloro-4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]pyrimidin-2-yl]amino]-5-methoxy-N-[(3S,4R)-3-methoxy-1-methylpiperidin-4-yl]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
2-chloro-4-[[5-chloro-4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]pyrimidin-2-yl]amino]-5-methoxy-N-[1-(oxan-4-yl)piperidin-4-yl]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
5-methoxy-2-methyl-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-(1-methylpiperidin-3-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
5-methoxy-2-methyl-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-[(3R)-1-methylpiperidin-3-yl]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
5-methoxy-2-methyl-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-[(3S)-1-methylpiperidin-3-yl]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
N-[2-(dimethylamino)ethyl]-5-methoxy-2-methyl-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
5-methoxy-N,2-dimethyl-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer
5-methoxy-2-methyl-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-(1-methylpiperidin-4-yl)benzamide	IC50	1 nM	US-8846689: Substituted pyrimidines for the treatment of diseases such as cancer

ChEMBL bioactivities

2482 potent at pChembl≥5 of 2622 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.15	IC50	0.07	nM	CHEMBL4554455
10.00	IC50	0.1	nM	CHEMBL5170906
9.97	IC50	0.1076	nM	CHEMBL5198068
9.93	IC50	0.1165	nM	CHEMBL5196177
9.91	IC50	0.1242	nM	CHEMBL5176233
9.81	IC50	0.1534	nM	CHEMBL5206909
9.79	IC50	0.161	nM	CHEMBL5187385
9.72	IC50	0.1924	nM	CHEMBL5190968
9.71	IC50	0.1941	nM	CHEMBL5177776
9.70	IC50	0.2	nM	DEFACTINIB
9.68	Kd	0.21	nM	NARMAFOTINIB
9.67	IC50	0.2131	nM	CHEMBL5176990
9.64	Ki	0.23	nM	CHEMBL4752642
9.56	IC50	0.275	nM	CHEMBL5204729
9.54	Kd	0.29	nM	CHEMBL3689069
9.53	IC50	0.2963	nM	CHEMBL5186801
9.52	IC50	0.3	nM	CHEMBL3692193
9.50	IC50	0.3146	nM	CHEMBL5178369
9.50	IC50	0.3146	nM	CHEMBL5199835
9.42	IC50	0.38	nM	CHEMBL5816460
9.41	IC50	0.39	nM	CHEMBL3692188
9.40	Ki	0.4	nM	CHEMBL4750273
9.40	IC50	0.4	nM	GSK-2256098
9.40	Ki	0.4	nM	GSK-2256098
9.36	Kd	0.44	nM	CHEMBL3692186
9.33	Kd	0.47	nM	CHEMBL3639910
9.33	Ki	0.47	nM	CHEMBL4783568
9.32	Kd	0.48	nM	CHEMBL3692201
9.31	Kd	0.49	nM	CHEMBL3692169
9.30	Kd	0.5	nM	DEFACTINIB
9.30	IC50	0.5	nM	CHEMBL487229
9.29	IC50	0.51	nM	CHEMBL3965256
9.29	IC50	0.51	nM	CHEMBL3892377
9.29	IC50	0.5143	nM	CHEMBL5177168
9.29	IC50	0.51	nM	CHEMBL5188373
9.24	Kd	0.57	nM	CHEMBL3692173
9.24	IC50	0.5794	nM	CHEMBL5192604
9.23	IC50	0.59	nM	CHEMBL5751180
9.23	IC50	0.59	nM	CHEMBL5779079
9.23	IC50	0.59	nM	CHEMBL5861426
9.23	IC50	0.59	nM	CHEMBL5812384
9.23	IC50	0.59	nM	CHEMBL5723019
9.23	IC50	0.59	nM	CHEMBL5778919
9.23	IC50	0.59	nM	CHEMBL4862042
9.23	IC50	0.59	nM	CHEMBL5974452
9.23	IC50	0.59	nM	CHEMBL5800727
9.23	IC50	0.59	nM	CHEMBL5776038
9.23	IC50	0.59	nM	CHEMBL5829684
9.23	IC50	0.59	nM	CHEMBL5908560
9.23	IC50	0.59	nM	CHEMBL5979700

PubChem BioAssay actives

987 with measured affinity, of 3986 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-(dimethylamino)ethyl 4-[4-[[4-[2-(methylcarbamoyl)anilino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzoyl]piperazine-1-carbodithioate	1555958: Inhibition of human recombinant N-terminal His-tagged FAK (393 to 698 residues) expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins by ADP-Glo assay	ic50	0.0001	uM
N-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]-2-diethoxyphosphorylacetamide	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0001	uM
5-chloro-4-N-(2-propan-2-ylsulfonylphenyl)-2-N-[4-(thiomorpholin-4-ylmethyl)phenyl]pyrimidine-2,4-diamine	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0001	uM
1-[[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]methyl]-N-[6-(hydroxyamino)-6-oxohexyl]piperidine-4-carboxamide	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0001	uM
1-[2-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]anilino]-2-oxoethyl]-N-[6-(hydroxyamino)-6-oxohexyl]piperidine-4-carboxamide	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0001	uM
2-[[5-chloro-2-[4-[[[3,4-dioxo-2-[2-(prop-2-enoylamino)ethylamino]cyclobuten-1-yl]amino]methyl]anilino]pyrimidin-4-yl]amino]-N-methylbenzamide	1699726: Covalent inhibition of recombinant human N-terminal His-tagged FAK (393 to 698 residues) expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) as substrate preincubated for 2 to 60 mins followed by substrate addition and measured after 1 hr by ADP-glo luminescence assay	ki	0.0002	uM
1-[[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]methyl]-N-(1-hydroxy-3-methylpentan-2-yl)piperidine-4-carboxamide	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0002	uM
[1-[[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]methyl]piperidin-4-yl]methanol	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0002	uM
1-[2-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]anilino]-2-oxoethyl]piperidine-4-carboxylic acid	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0002	uM
1-[[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]methyl]-N-(2-hydroxyethyl)piperidine-4-carboxamide	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0002	uM
1-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]-N-[6-(hydroxyamino)-6-oxohexyl]piperidine-4-carboxamide	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0002	uM
5-chloro-2-N-[4-(diethoxyphosphorylmethyl)phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0003	uM
1-[[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]methyl]piperidine-4-carboxylic acid	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0003	uM
methyl 6-[[1-[2-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]anilino]-2-oxoethyl]piperidine-4-carbonyl]amino]hexanoate	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0003	uM
2-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenoxy]-1-morpholin-4-ylethanone	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0003	uM
2-[[5-chloro-2-[4-[[[2-[2-[[(E)-2-cyano-3-cyclopropylprop-2-enoyl]amino]ethylamino]-3,4-dioxocyclobuten-1-yl]amino]methyl]anilino]pyrimidin-4-yl]amino]-N-methylbenzamide	1699726: Covalent inhibition of recombinant human N-terminal His-tagged FAK (393 to 698 residues) expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) as substrate preincubated for 2 to 60 mins followed by substrate addition and measured after 1 hr by ADP-glo luminescence assay	ki	0.0004	uM
2-[[5-chloro-2-[(5-methyl-2-propan-2-ylpyrazol-3-yl)amino]-4-pyridinyl]amino]-N-methoxybenzamide	1755626: Inhibition of FAK (unknown origin)	ic50	0.0004	uM
N-[3-[[[2-(3-bromoanilino)-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]-2-pyridinyl]-N-prop-2-enylmethanesulfonamide	1333746: Inhibition of NH2-terminal His6-tagged FAK kinase domain (410 to 689 residues) (unknown origin) expressed in baculovirus infected sf9 cells using p(Glu/Tyr) as substrate in presence of ATP	ic50	0.0005	uM
N-[3-[[[2-(3-bromo-4-morpholin-4-ylanilino)-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]-2-pyridinyl]-N-prop-2-enylmethanesulfonamide	1333746: Inhibition of NH2-terminal His6-tagged FAK kinase domain (410 to 689 residues) (unknown origin) expressed in baculovirus infected sf9 cells using p(Glu/Tyr) as substrate in presence of ATP	ic50	0.0005	uM
5-bromo-4-N-(5-dimethylphosphoryl-2,3-dihydro-1,4-benzodioxin-6-yl)-2-N-[2-methoxy-4-[4-[3-(methoxymethyl)azetidin-1-yl]piperidin-1-yl]-5-methylphenyl]pyrimidine-2,4-diamine	1862893: Inhibition of FAK (unknown origin)	ic50	0.0005	uM
2-[[5-chloro-2-[4-[[[2-[2-[[(E)-2-cyano-4-methylpent-2-enoyl]amino]ethylamino]-3,4-dioxocyclobuten-1-yl]amino]methyl]anilino]pyrimidin-4-yl]amino]-N-methylbenzamide	1699726: Covalent inhibition of recombinant human N-terminal His-tagged FAK (393 to 698 residues) expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) as substrate preincubated for 2 to 60 mins followed by substrate addition and measured after 1 hr by ADP-glo luminescence assay	ki	0.0005	uM
methyl 6-[[1-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]piperidine-4-carbonyl]amino]hexanoate	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0005	uM
N-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	1425142: 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	0.0005	uM
N-methyl-N-[2-[[[2-[(1-oxo-2,3-dihydroisoindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide	410184: Inhibition of GST-tagged FAK assessed as inhibition of poly-Glu-Tyr phosphorylation	ic50	0.0005	uM
ethyl 1-[[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]methyl]piperidine-4-carboxylate	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0006	uM
N-methyl-4-[[4-[[2-[methyl(methylsulfonyl)amino]-3-pyridinyl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	1755641: Inhibition of human FAK	ic50	0.0006	uM
N-methyl-N-[2-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide	2200421: Inhibition of full-length FAK (unknown origin) with N-terminal NanoLuc-fusion expressed in HEK293T cells by NanoBRET assay	ki	0.0009	uM
N-methyl-N-[2-[[[2-(4-methylsulfonylanilino)-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide	410184: Inhibition of GST-tagged FAK assessed as inhibition of poly-Glu-Tyr phosphorylation	ic50	0.0009	uM
N-methyl-N-[3-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]-2-pyridinyl]methanesulfonamide	1425142: 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
1-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]piperidine-4-carboxylic acid	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0010	uM
N-[2-[[[2-[(2,2-dioxo-1,3-dihydro-2,1-benzothiazol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]phenyl]-N-methylmethanesulfonamide	410184: Inhibition of GST-tagged FAK assessed as inhibition of poly-Glu-Tyr phosphorylation	ic50	0.0010	uM
2-fluoro-5-methoxy-4-[[4-[(2-methyl-3-oxo-1H-isoindol-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-(1-methylpiperidin-4-yl)benzamide	1978047: Inhibition of FAK (unknown origin)	ic50	0.0010	uM
2-[[5-chloro-2-[[(6R)-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1-methoxy-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl]amino]pyrimidin-4-yl]amino]-N-methylbenzamide	1319069: Inhibition of human FAK expressed in baculovirus after 30 mins using biotinyl-amino-hexanoyl-EQEDEPEGDYFEWLE-amide as substrate by TRF assay	ic50	0.0010	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	624729: Binding constant for FAK kinase domain	kd	0.0011	uM
16-methylsulfonyl-6-(trifluoromethyl)-2,4,8,14,16,25-hexazatetracyclo[18.3.1.13,7.010,15]pentacosa-1(23),3,5,7(25),10(15),11,13,20(24),21-nonaene	1333746: Inhibition of NH2-terminal His6-tagged FAK kinase domain (410 to 689 residues) (unknown origin) expressed in baculovirus infected sf9 cells using p(Glu/Tyr) as substrate in presence of ATP	ic50	0.0013	uM
5-chloro-2-N-[4-(3-morpholin-4-ylpropylsulfanyl)phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0013	uM
ethyl 1-[2-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]anilino]-2-oxoethyl]piperidine-4-carboxylate	1854514: Inhibition of recombinant human FAK (393 to 698 residues) using poly (4:1 Glu, Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo reagent based luminescent assay	ic50	0.0014	uM
2-[[2-(2-methoxy-4-morpholin-4-ylanilino)-5-(trifluoromethyl)pyrimidin-4-yl]amino]-N-methylbenzamide	1978048: Inhibition of GST-fused FAK (411 to 686 residues)(unknown origin) expressed in baculovirus expression system using poly(Glu:Tyr) as substrate incubated for 5 mins in presence of ATP by K-LISA screening assay	ic50	0.0015	uM
2-[[2-(2-methoxy-4-morpholin-4-ylanilino)-5-(trifluoromethyl)-4-pyridinyl]amino]-N-methylbenzamide	1684841: Inhibition of GST-FAK catalytic domain region (411-686) (unknown origin) expressed in baculovirus infected Sf9 cells by spectrophotometry	ic50	0.0015	uM
3-methoxy-4-[[4-[(3-oxo-1,2-dihydroinden-4-yl)oxy]-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-N-piperidin-4-ylbenzamide	1899255: Inhibition of FAK (unknown origin) using Fluorescein-Poly GAT as substrate incubated for 30 mins and measured after 60 mins by Lanthascreen assay	ic50	0.0019	uM
4-[[4-(2-methoxyanilino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-N-methylbenzamide	1765209: Inhibition of FAK (unknown origin) incubated for 40 mins by HTRF assay	ic50	0.0019	uM
N-methyl-N-[3-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide	410184: Inhibition of GST-tagged FAK assessed as inhibition of poly-Glu-Tyr phosphorylation	ic50	0.0019	uM
7-[[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]-4-methyl-2,3-dihydroinden-1-one	1899255: Inhibition of FAK (unknown origin) using Fluorescein-Poly GAT as substrate incubated for 30 mins and measured after 60 mins by Lanthascreen assay	ic50	0.0020	uM
2-[[5-chloro-2-[[(6S)-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1-methoxy-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl]amino]pyrimidin-4-yl]amino]-N-methylbenzamide	1319069: Inhibition of human FAK expressed in baculovirus after 30 mins using biotinyl-amino-hexanoyl-EQEDEPEGDYFEWLE-amide as substrate by TRF assay	ic50	0.0020	uM
N-[2-[[5-chloro-2-[[1-methoxy-6-(4-methylpiperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl]amino]pyrimidin-4-yl]amino]phenyl]-N-methylmethanesulfonamide	1319069: Inhibition of human FAK expressed in baculovirus after 30 mins using biotinyl-amino-hexanoyl-EQEDEPEGDYFEWLE-amide as substrate by TRF assay	ic50	0.0022	uM
N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(8-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide	2134069: Inhibition of FAK (unknown origin)	ic50	0.0022	uM
N-[2-[[5-chloro-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-1-methoxy-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl]amino]pyrimidin-4-yl]amino]phenyl]-N-methylmethanesulfonamide	1319069: Inhibition of human FAK expressed in baculovirus after 30 mins using biotinyl-amino-hexanoyl-EQEDEPEGDYFEWLE-amide as substrate by TRF assay	ic50	0.0024	uM
2-[[5-chloro-2-[4-[[[2-[2-[[(E)-2-cyanopent-2-enoyl]amino]ethylamino]-3,4-dioxocyclobuten-1-yl]amino]methyl]anilino]pyrimidin-4-yl]amino]-N-methylbenzamide	1699725: Inhibition of recombinant human N-terminal His-tagged FAK (393 to 698 residues) expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) as substrate measured after 1 hr by ADP-glo luminescence assay	ic50	0.0025	uM
4-methyl-7-[[2-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]-2,3-dihydroinden-1-one	1899255: Inhibition of FAK (unknown origin) using Fluorescein-Poly GAT as substrate incubated for 30 mins and measured after 60 mins by Lanthascreen assay	ic50	0.0025	uM
2-[[5-chloro-2-[4-(2-morpholin-4-yl-2-oxoethyl)sulfanylanilino]pyrimidin-4-yl]amino]-N-methylbenzamide	1551255: Inhibition of human recombinant N-terminal His-tagged FAK (393 to 698 residues) expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) peptide substrate incubated for 60 mins by ADP-Glo assay	ic50	0.0026	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	7
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	6
Tetradecanoylphorbol Acetate	decreases reaction, increases phosphorylation, affects cotreatment, increases reaction, increases expression (+1 more)	5
bisphenol A	affects reaction, affects cotreatment, increases phosphorylation	4
Resveratrol	increases phosphorylation, affects localization, affects binding, increases reaction, decreases expression (+1 more)	4
U 0126	decreases reaction, increases phosphorylation, decreases expression	3
6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one	affects localization, affects reaction, decreases reaction, increases phosphorylation, decreases phosphorylation	3
Carbamazepine	affects expression, decreases activity	3
Cisplatin	decreases expression	3
Endosulfan	decreases expression, increases phosphorylation	3
Fluorouracil	affects expression, decreases phosphorylation, decreases response to substance	3
Plant Extracts	decreases phosphorylation, increases reaction, decreases expression	3
Quercetin	decreases phosphorylation, decreases reaction, increases phosphorylation, decreases expression	3
Tretinoin	increases cleavage, affects binding, decreases reaction, increases reaction, increases activity (+2 more)	3
Cadmium Chloride	decreases expression, increases phosphorylation, increases abundance, affects reaction	3
geldanamycin	decreases phosphorylation, increases degradation	2
methylmercuric chloride	decreases expression	2
sodium arsenite	decreases expression, increases expression	2
oxophenylarsine	affects cotreatment, decreases reaction, increases phosphorylation, decreases expression	2
cordycepin	decreases expression, decreases reaction, decreases phosphorylation	2
perfluorooctane sulfonic acid	decreases expression, decreases response to substance	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases phosphorylation, increases reaction	2
deguelin	decreases expression, increases expression	2
benzyloxycarbonyl-valyl-alanyl-aspartic acid	increases degradation, decreases reaction, increases cleavage, increases abundance, increases activity (+1 more)	2
1,2,4,5-benzenetetraamine	decreases expression, decreases reaction, increases phosphorylation, decreases phosphorylation, increases reaction	2
CRT 0066101	increases expression, decreases expression, decreases reaction	2
Dasatinib	decreases phosphorylation	2
Wortmannin	affects cotreatment, decreases reaction, increases phosphorylation, increases reaction	2
Zoledronic Acid	increases expression, decreases phosphorylation	2
Fulvestrant	affects cotreatment, decreases methylation, increases degradation	2

ChEMBL screening assays

990 unique, capped per target: 989 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1019637	Binding	Inhibition of PTK2 at 1 uM	Pyranonaphthoquinone lactones: a new class of AKT selective kinase inhibitors alkylate a regulatory loop cysteine. — J Med Chem
CHEMBL1963801	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PTK2	PubChem BioAssay data set

Cellosaurus cell lines

9 cell lines: 7 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3FA	Abcam HEK293T PTK2 KO	Transformed cell line	Female
CVCL_B7Z0	Abcam Raji PTK2 KO	Cancer cell line	Male
CVCL_B9ZR	Abcam THP-1 PTK2 KO	Cancer cell line	Male
CVCL_C7BF	Abcam PC-3 PTK2 KO	Cancer cell line	Male
CVCL_D7YW	Ubigene A-549 PTK2 KO	Cancer cell line	Male
CVCL_D8U8	Ubigene HCT 116 PTK2 KO	Cancer cell line	Male
CVCL_D9Q1	Ubigene HEK293 PTK2 KO	Transformed cell line	Female
CVCL_E0M7	Ubigene HeLa PTK2 KO	Cancer cell line	Female
CVCL_F1RJ	HyCyte MCF-7 KO-hPTK2	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
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