ILK

Summary

ILK (integrin linked kinase, HGNC:6040) is a protein-coding gene on chromosome 11p15.4, encoding Scaffold protein ILK (Q13418). Scaffold protein which mediates protein-protein interactions during a range of cellular events including focal adhesion assembly, cell adhesion and cell migration. It is a selective cancer dependency (DepMap: 30.3% of cell lines).

This gene encodes a protein with a kinase-like domain and four ankyrin-like repeats. The encoded protein associates at the cell membrane with the cytoplasmic domain of beta integrins, where it regulates integrin-mediated signal transduction. Activity of this protein is important in the epithelial to mesenchymal transition, and over-expression of this gene is implicated in tumor growth and metastasis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3611 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy (Limited, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 359 total
• Phenotypes (HPO): 1
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 30.3% of screened cell lines
• MANE Select transcript: NM_004517

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6040
Approved symbol	ILK
Name	integrin linked kinase
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166333
Ensembl biotype	protein_coding
OMIM	602366
Entrez	3611

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 27 protein_coding, 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000299421, ENST00000396751, ENST00000420936, ENST00000524735, ENST00000526114, ENST00000526318, ENST00000526711, ENST00000527121, ENST00000528784, ENST00000528995, ENST00000530016, ENST00000532063, ENST00000534565, ENST00000534706, ENST00000537806, ENST00000627400, ENST00000875220, ENST00000875221, ENST00000875222, ENST00000875223, ENST00000875224, ENST00000875225, ENST00000875226, ENST00000875227, ENST00000875228, ENST00000918172, ENST00000918173, ENST00000918174, ENST00000951914, ENST00000951915, ENST00000951916, ENST00000951917, ENST00000951918, ENST00000951919, ENST00000951920

RefSeq mRNA: 5 — MANE Select: NM_004517 NM_001014794, NM_001014795, NM_001278441, NM_001278442, NM_004517

CCDS: CCDS60712, CCDS60713, CCDS7768

Canonical transcript exons

ENST00000299421 — 13 exons

Exon	Start	End
ENSE00001188614	6604180	6604360
ENSE00003469064	6608046	6608211
ENSE00003576399	6608884	6608967
ENSE00003577304	6608394	6608489
ENSE00003579110	6609724	6609845
ENSE00003586971	6608694	6608790
ENSE00003656912	6609936	6610035
ENSE00003657452	6609299	6609408
ENSE00003684724	6609512	6609639
ENSE00003691494	6609071	6609156
ENSE00003713337	6610148	6610278
ENSE00003901396	6610462	6610870
ENSE00003901740	6603774	6603822

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.0082 / max 507.8405, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112867	38.2559	1822
112866	2.1094	1382
112869	1.5579	886
112868	1.0190	688
112871	0.0660	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of uterus	UBERON:0009853	99.43	gold quality
popliteal artery	UBERON:0002250	99.39	gold quality
tibial artery	UBERON:0007610	99.39	gold quality
right coronary artery	UBERON:0001625	99.38	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.37	gold quality
aorta	UBERON:0000947	99.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.36	gold quality
ascending aorta	UBERON:0001496	99.34	gold quality
thoracic aorta	UBERON:0001515	99.34	gold quality
descending thoracic aorta	UBERON:0002345	99.34	gold quality
lower esophagus	UBERON:0013473	99.34	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.27	gold quality
saphenous vein	UBERON:0007318	99.21	gold quality
left coronary artery	UBERON:0001626	99.15	gold quality
coronary artery	UBERON:0001621	99.14	gold quality
left uterine tube	UBERON:0001303	99.13	gold quality
mucosa of stomach	UBERON:0001199	99.12	gold quality
smooth muscle tissue	UBERON:0001135	99.11	gold quality
myometrium	UBERON:0001296	98.99	gold quality
endocervix	UBERON:0000458	98.79	gold quality
apex of heart	UBERON:0002098	98.78	gold quality
stromal cell of endometrium	CL:0002255	98.74	gold quality
blood vessel layer	UBERON:0004797	98.73	gold quality
fundus of stomach	UBERON:0001160	98.46	gold quality
heart left ventricle	UBERON:0002084	98.42	gold quality
right atrium auricular region	UBERON:0006631	98.40	gold quality
cardiac ventricle	UBERON:0002082	98.38	gold quality
right ovary	UBERON:0002118	98.38	gold quality
tibial nerve	UBERON:0001323	98.32	gold quality
heart	UBERON:0000948	98.31	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	40.03
E-CURD-112	yes	37.41
E-HCAD-4	yes	37.29
E-HCAD-1	yes	32.29
E-CURD-122	yes	24.01
E-MTAB-8410	yes	22.60
E-MTAB-9221	yes	17.39
E-HCAD-10	yes	16.97
E-MTAB-9067	yes	13.33
E-HCAD-11	yes	10.34
E-ANND-3	yes	10.29
E-GEOD-134144	yes	8.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ERG, ETS1, FOS, FOXC1, HIF1A, JUN, KLF5, LIMS1, NFKB, PARP1, PPARD, REL, RELA, SNAI1, SP1, TBP, TFAP2A, TP53, TWIST1, TWIST2

miRNA regulators (miRDB)

25 targeting ILK, 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-4425	100.00	67.59	1049
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-758-3P	98.42	68.60	1122
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-1470	98.11	63.53	399
HSA-MIR-6757-5P	98.08	65.50	724
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-624-5P	96.00	68.88	728

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 30.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Role of integrin-linked kinase in leukocyte recruitment (PMID:11856758)
• Integrin-linked kinase phosphorylates the myosin phosphatase target subunit at the inhibitory site in platelet cytoskeleton. (PMID:11931630)
• Ionizing radiation strongly induced the expression of functional beta1-integrin and ILK in the two lung cancer cell lines, A549 and SKMES1. (PMID:12020426)
• Integrin-linked kinase transiently associates with and phosphorylates beta3 in a PI3-kinase dependent manner (PMID:12152651)
• Ganglioside loss promotes survival primarily by activating integrin-linked kinase/Akt without phosphoinositide 3-OH kinase signaling. (PMID:12164932)
• the ILK-affixin complex has a role in integrin-cytoskeleton linkage during platelet aggregation (PMID:12372433)
• Assembly of the PINCH-ILK-CH-ILKBP complex precedes and is essential for localization of each component to cell-matrix adhesion sites (PMID:12432066)
• role in alpha(v)integrin in regulating cell proliferation in ovarian cancer cells (PMID:12642872)
• Cells that are depleted of this enzyme undergo extensive apoptosis. (PMID:12654898)
• role in protein kinase B/Akt activation. (PMID:12686550)
• Overexpression of integrin-linked kinase is associated with sporadic human colon cancer (PMID:12771992)
• Cell adhesion to the extracellular matrix protein fibronectin modulates radiation-dependent G2 phase arrest and involve this enzyme in vitro. (PMID:12778079)
• ILK has a role in oncogenic transformation and progression to invasive and metastatic phenotypes [review] (PMID:12884912)
• ILK is a critical mediator for tubular EMT and likely plays a crucial role in the pathogenesis of chronic renal fibrosis (PMID:12925691)
• ILK kinase activity, or expression, results in the inhibition of cell attachment, cell migration, F-actin organization (PMID:12960424)
• PINCH1 and ILK are essential for prompt cell spreading and motility; PINCH1 and ILK, like alpha-parvin, are crucial for cell survival; PINCH1 and ILK are required for optimal activating phosphorylation of PKB/Akt of the survival pathway (PMID:14551191)
• Increased expression of integrin-linked kinase is correlated with melanoma progression (PMID:14555513)
• integrin-lined kinase plays an important role in vascular morphogenesis (PMID:14679308)
• essential role of ILK in two key aspects of tumor angiogenesis: VEGF expression by tumor cells and VEGF-stimulated blood vessel formation (PMID:14749128)
• Taken together, these data suggest that PI3K-ILK-Akt pathway that is independent of the TGFbeta-induced Smad pathway is required for TGFbeta-mediated epithelial to mesenchymal transition. (PMID:15044083)
• 59 kDa immunoreactive integrin-linked kinase is upreguated in the blood and peritoneal fluid of ovarian cancer patients before, but not after chemotherapy (PMID:15073119)
• ILK regulates alpha 2 beta 1 in HEL cells, is activated in platelets and associates with beta 1-integrins (PMID:15304053)
• Data provide evidence that ILK signaling modulates the cellular radiation response involving diverse signaling pathways and through changes in f-actin-based processes such as focal adhesion formation, cell adhesion, and spreading. (PMID:15313908)
• loss of ParvB expression is a novel mechanism for upregulating ILK activity in tumors (PMID:15467740)
• ILK overexpression protects vascular endothelium cells and progenitor cells from anchorage- or nutrient-deprived stress and enhances neovascularization (PMID:15802621)
• Finding suggests that therapies directed against ILK and its downstream signaling targets may have the potential to enhance the efficacy of gemcitabine-based chemotherapy. (PMID:15867245)
• Dissociation of ILK from Hsp90 shortened its half-life by promoting proteasome-dependent degradation (PMID:15882985)
• matrix-derived mechanical forces sensed by beta1 integrin are capable of modulating ILK activity which regulates fibroblast viability via an Akt-dependent mechanism (PMID:15905178)
• Strong expression of ILK in cancerous tissues is involved with aggressive capability in pancreatic cancer. (PMID:16407822)
• ILK is a critical effector in a signaling pathway necessary for granule cell proliferation and cerebellar development. (PMID:16421303)
• ILK may act as a pro-survival factor and play a role in protecting mesangial cells from hyperglycaemic osmotic stress (PMID:16611685)
• functions as a downstream mediator of the ET-1/ET(A)R axis to potentiate aggressive cellular behavior in ovarian cancer cells. (PMID:16648553)
• ILK activity can modulate acute Wnt3a mediated beta-catenin phosphorylation, stabilization and nuclear activation in a PI3K-independent manner. (PMID:16799642)
• Endogenous ILK is a novel and physiological upstream responder of numerous intracellular molecules involved in hypoxic stress in endothelial cellss and may control the recruitment of peogenitor cells to ischemic tissue. (PMID:16818815)
• ILK may participate in invasion and metastasis of laryngeal squamous cell carcinoma. (PMID:16836071)
• Review highlights the role of integrin-linked kinase (ILK) as a novel component of the cardiac mechanical stretch sensor. (PMID:16951248)
• Cell adhesion and/or its related molecular basis regulate epigenetic mechanisms leading to a loss of ILK transcription, which in turn regulates cell adhesion property in a feedback linkage. (PMID:16987993)
• R-Ras and ILK have roles upstream of GSK-3beta in the regulation of neuronal polarity (PMID:17107957)
• Identification of ILK as a player in hypoxia survival signaling employed by cancer cells further validates ILK as a unique target for cancer therapy. (PMID:17143519)
• This study suggests that ILK serves as a key mediator in TGFbeta1 regulation of uPA/PAI-1 system critical for the invasiveness of human ovarian cancer cells. And ILK is a potential target for cancer therapy. (PMID:17187779)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ilk	ENSDARG00000056964
mus_musculus	Ilk	ENSMUSG00000030890
rattus_norvegicus	Ilk	ENSRNOG00000018993
drosophila_melanogaster	Ilk	FBGN0028427
caenorhabditis_elegans		WBGENE00003931

Paralogs (23): MAP3K9 (ENSG00000006432), TESK2 (ENSG00000070759), MAP3K13 (ENSG00000073803), ARAF (ENSG00000078061), MAP3K20 (ENSG00000091436), RIPK2 (ENSG00000104312), LIMK1 (ENSG00000106683), TESK1 (ENSG00000107140), TNNI3K (ENSG00000116783), RIPK3 (ENSG00000129465), MAP3K10 (ENSG00000130758), RAF1 (ENSG00000132155), RIPK1 (ENSG00000137275), MAP3K12 (ENSG00000139625), KSR1 (ENSG00000141068), MAP3K21 (ENSG00000143674), BRAF (ENSG00000157764), MLKL (ENSG00000168404), KSR2 (ENSG00000171435), MOS (ENSG00000172680), MAP3K11 (ENSG00000173327), LIMK2 (ENSG00000182541), LRRK2 (ENSG00000188906)

Protein

Protein identifiers

Scaffold protein ILK — Q13418 (reviewed: Q13418)

Alternative names: ILK-1, ILK-2, Inactive integrin-linked kinase, p59ILK

All UniProt accessions (6): A0A087WW45, A0A087WWY6, Q13418, A0A0A0MTH3, E9PQ52, V9HWF0

UniProt curated annotations — full annotation on UniProt →

Function. Scaffold protein which mediates protein-protein interactions during a range of cellular events including focal adhesion assembly, cell adhesion and cell migration. Regulates integrin-mediated signal transduction by contributing to inside-out integrin activation. Recruits PARVA and LIMS1/PITCH to form the heterotrimeric IPP (ILK-PINCH-PARVIN) complex which binds to F-actin via the C-terminal tail of LIMS1 and the N-terminal region of PARVA, promoting F-actin filament bundling, a process required to generate force for actin cytoskeleton reorganization and subsequent dynamic cell adhesion events such as cell spreading and migration. Binding to PARVA promotes effective assembly of ILK into focal adhesions while PARVA-bound ILK can simultaneously engage integrin-beta cytoplasmic tails to mediate cell adhesion. Plays a role with PARVG in promoting the cell adhesion and spreading of leukocytes. Acts as an upstream effector of both AKT1/PKB and GSK3. Mediates trafficking of caveolae to the cell surface in an ITGB1-dependent manner by promoting the recruitment of IQGAP1 to the cell cortex which cooperates with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane. Required for the maintenance of mitotic spindle integrity by promoting phosphorylation of TACC3 by AURKA. Associates with chromatin and may act as a negative regulator of transcription when located in the nucleus.

Subunit / interactions. Component of the heterotrimeric IPP (ILK-PINCH-PARVIN) complex composed of ILK, LIMS1/PINCH and PARVA; the complex binds to F-actin via the C-terminal tail of LIMS1 and the N-terminal region of PARVA, promoting F-actin filament bundling. Formation of the IPP complex is dependent on protein kinase C and precedes integrin-mediated cell adhesion and spreading. ILK also interacts with LIMS2/PINCH2 and with PARVB and PARVG which may substitute for LIMS1 and PARVA in the IPP complex; PARVA and PARVB compete for the same binding site. Interaction with PARVG promotes the establishment of cell polarity required for leukocyte migration. Interacts with the cytoplasmic domain of integrin ITGB1 and may also interact with integrins ITGB2, ITGB3 and/or ITGB5. Interacts probably also with TGFB1I1. Interacts (via ANK repeats) with EPHA1 (via SAM domain); stimulated by EFNA1 but independent of the kinase activity of EPHA1. Interacts with FERMT2. Interacts with LIMD2; leading to activate the protein kinase activity. Interacts with PXN/PAXILLIN (via LD motif 4). Interacts with CCDC25 (via cytoplasmic region); initiating the ILK-PARVB cascade to induce cytoskeleton rearrangement and directional migration of cells. Interacts with IQGAP1; the interaction is required for localization of IQGAP1 to the cell cortex.

Subcellular location. Cell junction. Focal adhesion. Cell membrane. Cell projection. Lamellipodium. Cytoplasm. Myofibril. Sarcomere. Nucleus. Cytoskeleton. Microtubule organizing center. Centrosome. Cell cortex.

Tissue specificity. Highly expressed in heart followed by skeletal muscle, pancreas and kidney. Weakly expressed in placenta, lung and liver.

Post-translational modifications. Phosphorylation by PAK1 modulates ILK subcellular location by promoting its nuclear export.

Domain organisation. The kinase domain is likely to have lost catalytic activity but retains ATP-binding activity. ATP structurally stabilizes the kinase domain and promotes stability of binding to PARVA as well as focal adhesion stability. The PH-like region is not required for assembly of the IPP complex or for localization of ILK to focal adhesions.

Similarity. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13418-1	1	yes
Q13418-2	2
Q13418-3	3

RefSeq proteins (5): NP_001014794, NP_001014795, NP_001265370, NP_001265371, NP_004508* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR035692	PK_ILK	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR051681	Ser/Thr_Kinases-Pseudokinases	Family

Pfam: PF07714, PF12796

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

UniProt features (80 total): helix 25, mutagenesis site 13, strand 11, binding site 10, repeat 5, modified residue 5, turn 3, splice variant 2, region of interest 2, chain 1, sequence variant 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
4HI8	X-RAY DIFFRACTION	1.2
4HI9	X-RAY DIFFRACTION	1.2
9TP9	X-RAY DIFFRACTION	1.45
9D5E	X-RAY DIFFRACTION	1.5
9D5F	X-RAY DIFFRACTION	1.5
9D5H	X-RAY DIFFRACTION	1.5
9D5I	X-RAY DIFFRACTION	1.5
9D5P	X-RAY DIFFRACTION	1.5
9TPD	X-RAY DIFFRACTION	1.5
9D5G	X-RAY DIFFRACTION	1.55
3F6Q	X-RAY DIFFRACTION	1.6
3KMU	X-RAY DIFFRACTION	1.8
3REP	X-RAY DIFFRACTION	1.8
6MIB	X-RAY DIFFRACTION	1.8
3IXE	X-RAY DIFFRACTION	1.9
3KMW	X-RAY DIFFRACTION	2
2KBX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13418-F1	88.13	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (10): 200; 202; 203; 204; 220; 270; 272; 279; 339; 341

Post-translational modifications (5): 1, 173, 186, 246, 426

Mutagenesis-validated functional residues (13):

Position	Phenotype
31	loss of interaction with lims1 and loss of localization to focal adhesions.
99	alters interaction with lims1.
173	severely reduces pak1-mediated phosphorylation and increases nuclear localization. reduced cell proliferation and cell m
181	no effect on pak1-mediated phosphorylation.
207	prevents binding of atp and mg(2+). does not affect binding to f-actin but dramatically impairs f-actin filament bundlin
220	reduced interaction with parva due to destabilization of ilk.
225	reduced interaction with parva. decreased focal adhesion assembly and reduced cell migration; when associated with a-349
228	no effect on pak1-mediated phosphorylation.
246	severely reduces pak1-mediated phosphorylation and increases nuclear and focal adhesion localization. reduced cell proli
349	reduced interaction with parva. decreased focal adhesion assembly and reduced cell migration; when associated with a-225
363	remains almost completely cytoplasmic with little nuclear localization.
400	results in nuclear accumulation of the protein and altered cell morphology.
402–403	abolishes binding to parva and impairs localization of ilk to focal adhesions.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-446343	Localization of the PINCH-ILK-PARVIN complex to focal adhesions
R-HSA-446353	Cell-extracellular matrix interactions

MSigDB gene sets: 295 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, BIOCARTA_PTEN_PATHWAY, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_RESPONSE_TO_PEPTIDE, GOBP_MEMBRANE_BIOGENESIS, GOBP_PLATELET_ACTIVATION, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_GLIAL_CELL_DEVELOPMENT, HSIAO_HOUSEKEEPING_GENES, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_NEUROGENESIS

GO Biological Process (32): cell morphogenesis (GO:0000902), branching involved in ureteric bud morphogenesis (GO:0001658), outflow tract morphogenesis (GO:0003151), mitotic spindle organization (GO:0007052), cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), positive regulation of cell population proliferation (GO:0008284), positive regulation of signal transduction (GO:0009967), fibroblast migration (GO:0010761), nerve development (GO:0021675), myelination in peripheral nervous system (GO:0022011), cell projection organization (GO:0030030), cell differentiation (GO:0030154), positive regulation of BMP signaling pathway (GO:0030513), tumor necrosis factor-mediated signaling pathway (GO:0033209), substrate adhesion-dependent cell spreading (GO:0034446), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of DNA-templated transcription (GO:0045893), neural precursor cell proliferation (GO:0061351), platelet aggregation (GO:0070527), caveola assembly (GO:0070836), protein localization to cell cortex (GO:0072697), positive regulation of canonical Wnt signaling pathway (GO:0090263), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026), negative regulation of neural precursor cell proliferation (GO:2000178), protein phosphorylation (GO:0006468), cell population proliferation (GO:0008283), anatomical structure morphogenesis (GO:0009653), Schwann cell development (GO:0014044)

GO Molecular Function (10): magnesium ion binding (GO:0000287), protein kinase activity (GO:0004672), signaling receptor binding (GO:0005102), integrin binding (GO:0005178), ATP binding (GO:0005524), protein kinase binding (GO:0019901), protein-macromolecule adaptor activity (GO:0030674), nucleotide binding (GO:0000166), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (16): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell cortex (GO:0005938), actin cytoskeleton (GO:0015629), membrane (GO:0016020), sarcomere (GO:0030017), lamellipodium (GO:0030027), cytoskeleton (GO:0005856), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cell-extracellular matrix interactions	1
Cell junction organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
anatomical structure morphogenesis	2
cell-substrate adhesion	2
protein binding	2
cytoplasm	2
cell periphery	2
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
heart morphogenesis	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
cell surface receptor signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
signal transduction	1
regulation of signal transduction	1
positive regulation of cell communication	1
positive regulation of signaling	1
positive regulation of response to stimulus	1
ameboidal-type cell migration	1
nervous system development	1
anatomical structure development	1
Schwann cell development	1
peripheral nervous system axon ensheathment	1
myelination	1
cellular component organization	1
cellular developmental process	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
intracellular signaling cassette	1
establishment or maintenance of apical/basal cell polarity	1
osteoblast differentiation	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

212 interactions, top by confidence:

A	B	Type	Score
ILK	PARVA	psi-mi:“MI:0915”(physical association)	0.970
RICTOR	MTOR	psi-mi:“MI:0914”(association)	0.970
PARVA	ILK	psi-mi:“MI:0915”(physical association)	0.970
LIMS1	ILK	psi-mi:“MI:0915”(physical association)	0.960
ILK	LIMS1	psi-mi:“MI:0407”(direct interaction)	0.960
ILK	LIMS1	psi-mi:“MI:0914”(association)	0.960
ILK	LIMS1	psi-mi:“MI:0915”(physical association)	0.960
LIMS1	ILK	psi-mi:“MI:0914”(association)	0.960
ILK	PARVG	psi-mi:“MI:0915”(physical association)	0.900
PARVG	ILK	psi-mi:“MI:0915”(physical association)	0.900
RSU1	LIMS1	psi-mi:“MI:0914”(association)	0.850
TRIM27	ILK	psi-mi:“MI:0915”(physical association)	0.670
ILK	TRIM27	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (495): RICTOR (Affinity Capture-MS), RICTOR (Affinity Capture-Western), ILK (Affinity Capture-Western), ILK (Affinity Capture-Western), RICTOR (Two-hybrid), ITGB1 (Two-hybrid), AKT1 (Affinity Capture-Western), TRIM27 (Two-hybrid), PARVA (Two-hybrid), PARVG (Two-hybrid), ILK (Affinity Capture-RNA), ILK (Affinity Capture-RNA), ILK (Affinity Capture-RNA), ABCF2 (Affinity Capture-MS), ADNP (Affinity Capture-MS)

ESM2 similar proteins: A2XFF4, A8XWC4, B8BBT7, F4IS56, O08680, O22558, O44997, O55222, O74536, P29318, P29319, P29320, P34208, P53355, P53356, P54645, P54646, P54758, P57044, Q02111, Q02723, Q09137, Q13131, Q13418, Q28948, Q2MHE4, Q2QXC6, Q3SWY2, Q54Y55, Q5EG47, Q5R5V4, Q5RD00, Q5RDH5, Q60629, Q61RA2, Q62413, Q80YE7, Q852Q0, Q852Q1, Q8BRK8

Diamond homologs: A0A509AIU5, A7E3S4, D3ZG83, O01700, O19004, O55222, P00532, P04049, P04627, P05625, P06782, P09560, P10398, P10533, P11345, P14056, P15056, P18160, P18161, P27636, P27966, P28028, P34908, P57044, P80192, P83104, Q00372, Q02779, Q04982, Q13418, Q1ZXD6, Q3SWY2, Q3U1V8, Q54H45, Q54H46, Q54JC7, Q54R58, Q54TA1, Q54TM7, Q54XY6

SIGNOR signaling

28 interactions.

A	Effect	B	Mechanism
ILK	“up-regulates activity”	PPP1R14C	phosphorylation
ILK	“up-regulates activity”	MYL12B	phosphorylation
PXN	up-regulates	ILK	binding
ILK	“up-regulates activity”	ILK	phosphorylation
ILK	up-regulates	NACA	phosphorylation
PAK1	up-regulates	ILK	phosphorylation
ILK	down-regulates	CFL1	phosphorylation
ILK	up-regulates	AKT1	phosphorylation
TWIST2	“down-regulates quantity by repression”	ILK	“transcriptional regulation”
TWIST1	“down-regulates quantity by repression”	ILK	“transcriptional regulation”
ILK	“down-regulates activity”	GSK3B	phosphorylation
ILK	“up-regulates activity”	PARVB	phosphorylation
ILK	“up-regulates activity”	AKT2	phosphorylation
ILK	“up-regulates activity”	SYNPO2	phosphorylation
ILK	up-regulates	AKT	phosphorylation
ILK	down-regulates	PPP1R12A	phosphorylation
ILK	“up-regulates activity”	PPP1R14A	phosphorylation
ILK	“up-regulates activity”	AKT	phosphorylation
ILK	“up-regulates activity”	AKT1	phosphorylation
ILK	“down-regulates activity”	PPP1R12A	phosphorylation
ILK	“up-regulates activity”	PPP1R14B	phosphorylation
ILK	“form complex”	“IPP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 140 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
Intrinsic Pathway for Apoptosis	7	20.9×	1e-05
HSF1-dependent transactivation	5	16.2×	1e-03
Apoptosis	7	12.0×	3e-04
Programmed Cell Death	7	10.5×	6e-04
Regulation of HSF1-mediated heat shock response	7	9.9×	7e-04
Regulation of actin dynamics for phagocytic cup formation	5	9.4×	6e-03
Transcriptional and post-translational regulation of MITF-M expression and activity	5	9.1×	6e-03
Toll Like Receptor TLR6:TLR2 Cascade	5	9.0×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
substrate adhesion-dependent cell spreading	6	16.1×	1e-03
endothelial cell migration	5	16.1×	3e-03
response to unfolded protein	5	11.8×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	178
Likely benign	151
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

1856 predictions. Top by Δscore:

Variant	Effect	Δscore
11:6604358:GGG:G	donor_gain	1.0000
11:6604359:GGG:G	donor_gain	1.0000
11:6608072:ACT:A	acceptor_gain	1.0000
11:6608072:ACTG:A	acceptor_gain	1.0000
11:6608374:T:A	acceptor_gain	1.0000
11:6608378:T:TA	acceptor_gain	1.0000
11:6608379:G:A	acceptor_gain	1.0000
11:6608383:A:AG	acceptor_gain	1.0000
11:6608383:AT:A	acceptor_gain	1.0000
11:6608383:ATG:A	acceptor_gain	1.0000
11:6608383:ATGG:A	acceptor_gain	1.0000
11:6608383:ATGGG:A	acceptor_gain	1.0000
11:6608384:T:G	acceptor_gain	1.0000
11:6608384:T:TA	acceptor_gain	1.0000
11:6608385:G:A	acceptor_gain	1.0000
11:6608393:GCT:G	acceptor_gain	1.0000
11:6608487:GAG:G	donor_gain	1.0000
11:6608488:AG:A	donor_gain	1.0000
11:6608489:GG:G	donor_gain	1.0000
11:6608490:G:C	donor_loss	1.0000
11:6608490:G:GG	donor_gain	1.0000
11:6608963:GCCCC:G	donor_gain	1.0000
11:6608965:CCCG:C	donor_loss	1.0000
11:6608966:CC:C	donor_gain	1.0000
11:6608966:CCGT:C	donor_loss	1.0000
11:6608967:CGTGA:C	donor_loss	1.0000
11:6608968:G:GG	donor_gain	1.0000
11:6608968:GTGAG:G	donor_loss	1.0000
11:6608969:T:G	donor_loss	1.0000
11:6608970:G:GG	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000443308 (11:6607580 C>A,G,T), RS1000835819 (11:6603746 G>C,T), RS1001394474 (11:6603883 G>A), RS1001645031 (11:6607961 G>C,T), RS1001718645 (11:6608272 A>C), RS1001828815 (11:6603228 C>T), RS1002070165 (11:6603039 T>C), RS1002721805 (11:6609741 A>G), RS1003234445 (11:6604122 C>G,T), RS1003237073 (11:6604717 A>G), RS1003404417 (11:6611182 C>CT), RS1003732256 (11:6611105 G>A,C), RS1003791517 (11:6605096 T>C,G), RS1003875386 (11:6604525 G>C,T), RS1003900254 (11:6606731 A>G)

Disease associations

OMIM: gene MIM:602366 | disease phenotypes: MIM:192600, MIM:256730

GenCC curated gene-disease

Disease	Classification	Inheritance
dilated cardiomyopathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dilated cardiomyopathy	Limited	AD

Mondo (5): familial hypertrophic cardiomyopathy (MONDO:0024573), neuronal ceroid lipofuscinosis (MONDO:0016295), cardiomyopathy (MONDO:0004994), long QT syndrome (MONDO:0002442), dilated cardiomyopathy (MONDO:0005021)

Orphanet (6): Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Neuronal ceroid lipofuscinosis (Orphanet:216), OBSOLETE: Infantile neuronal ceroid lipofuscinosis (Orphanet:79263), Rare cardiomyopathy (Orphanet:167848), Dilated cardiomyopathy (Orphanet:217604), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001644	Dilated cardiomyopathy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5247 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 150,373 (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
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL2079588	TELATINIB	2	1,279

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — ILK subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 22 [PMID: 21823616]	Inhibition	6.22	pIC50

Binding affinities (BindingDB)

151 measured of 151 human assays (151 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-5-fluoro-1,3-benzothiazole-6-sulfonamide	IC50	7 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-1,3-benzothiazole-6-sulfonamide	IC50	10 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
5-(3-aminopropyl)-4-(1,3-benzothiazol-2-yl)-1H-pyrazol-3-amine	IC50	10 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(5-amino-1H-pyrazol-4-yl)-5-fluoro-1,3-benzothiazole-6-sulfonamide	IC50	20 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(1,3-benzothiazol-2-yl)-5-[3-(methylamino)propyl]-1H-pyrazol-3-amine	IC50	20 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
3-N-(2-aminoethyl)-4-(1,3-benzothiazol-2-yl)-1H-pyrazole-3,5-diamine	IC50	20 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-5-fluoro-N-methyl-1,3-benzothiazole-6-sulfonamide	IC50	40 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-4-fluoro-1,3-benzothiazole-6-sulfonamide	IC50	40 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-N-(pyridin-4-ylmethyl)-1,3-benzothiazole-6-sulfonamide	IC50	40 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(5-fluoro-6-methoxy-1,3-benzothiazol-2-yl)-5-(furan-2-yl)-1H-pyrazol-3-amine	IC50	40 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(5-fluoro-1,3-benzothiazol-2-yl)-5-methyl-1H-pyrazol-3-amine	IC50	40 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-5-fluoro-N-(2-hydroxyethyl)-1,3-benzothiazole-6-sulfonamide	IC50	50 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-pyridin-4-yl-1H-pyrazol-4-yl)-1,3-benzothiazole-6-sulfonamide	IC50	50 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(5-fluoro-6-methyl-1,3-benzothiazol-2-yl)-1H-pyrazol-5-amine	IC50	50 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
methyl 2-(3-amino-5-methyl-1H-pyrazol-4-yl)-5-fluoro-1,3-benzothiazole-6-carboxylate	IC50	60 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(5-amino-1H-pyrazol-4-yl)-N-methyl-1,3-benzothiazole-6-sulfonamide	IC50	60 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(5-fluoro-6-methoxy-1,3-benzothiazol-2-yl)-5-methyl-1H-pyrazol-3-amine	IC50	60 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(1,3-benzothiazol-2-yl)-5-piperidin-4-yl-1H-pyrazol-3-amine	IC50	60 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-4,5,6-trifluoro-1,3-benzothiazole-7-sulfonamide	IC50	70 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-N-methyl-1,3-benzothiazole-6-sulfonamide	IC50	70 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(5-fluoro-6-methoxy-1,3-benzothiazol-2-yl)-3-piperazin-1-yl-1H-pyrazol-5-amine	IC50	70 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-N-(2,2,2-trifluoroethyl)-1,3-benzothiazole-6-sulfonamide	IC50	90 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
[2-(3-amino-5-methyl-1H-pyrazol-4-yl)-5-fluoro-1,3-benzothiazol-6-yl]methanol	IC50	100 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-[[2-(3-amino-5-methyl-1H-pyrazol-4-yl)-1,3-benzothiazol-6-yl]methylamino]ethanol	IC50	100 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(5-fluoro-6-methoxy-1,3-benzothiazol-2-yl)-5-(1,2-oxazol-5-yl)-1H-pyrazol-3-amine	IC50	100 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(1,3-benzothiazol-2-yl)-5-[4-(methylamino)butyl]-1H-pyrazol-3-amine	IC50	100 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(1,3-benzothiazol-2-yl)-5-(furan-2-yl)-1H-pyrazol-3-amine	IC50	100 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(1,3-benzothiazol-2-yl)-5-pyridin-4-yl-1H-pyrazol-3-amine	IC50	100 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
5-(4-aminophenyl)-4-(1,3-benzothiazol-2-yl)-1H-pyrazol-3-amine	IC50	100 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-5-fluoro-N-(pyridin-4-ylmethyl)-1,3-benzothiazole-6-sulfonamide	IC50	130 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-5-fluoro-N-(2-hydroxyethyl)-1,3-benzothiazole-4-sulfonamide	IC50	150 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(1,3-benzothiazol-2-yl)-3-N-[2-(ethylamino)ethyl]-1H-pyrazole-3,5-diamine	IC50	150 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(1,3-benzothiazol-2-yl)-3-piperazin-1-yl-1H-pyrazol-5-amine	IC50	190 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(1,3-benzothiazol-2-yl)-N-[2-(1H-imidazol-5-yl)ethyl]-1H-pyrazol-5-amine	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-1,3-benzothiazol-5-ol	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-N-(2-hydroxyethyl)-1,3-benzothiazole-6-sulfonamide	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-N-[2-(4-aminophenyl)ethyl]-1,3-benzothiazole-6-sulfonamide	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-N-[2-(1H-imidazol-5-yl)ethyl]-1,3-benzothiazole-6-sulfonamide	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
3-[3-amino-4-(1,3-benzothiazol-2-yl)-1H-pyrazol-5-yl]propan-1-ol	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(5-fluoro-6-methoxy-1,3-benzothiazol-2-yl)-5-pyridin-4-yl-1H-pyrazol-3-amine	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(5-fluoro-6-methoxy-1,3-benzothiazol-2-yl)-3-N-[2-(1H-imidazol-5-yl)ethyl]-1H-pyrazole-3,5-diamine	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(6-bromo-5-fluoro-1,3-benzothiazol-2-yl)-5-methyl-1H-pyrazol-3-amine	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-[6-[(dimethylamino)methyl]-1,3-benzothiazol-2-yl]-5-methyl-1H-pyrazol-3-amine	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(6-fluoro-1,3-benzothiazol-2-yl)-1H-pyrazol-5-amine	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(6-methoxy-1,3-benzothiazol-2-yl)-3-piperazin-1-yl-1H-pyrazol-5-amine	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
4-(1,3-benzothiazol-2-yl)-5-[3-(dimethylamino)propyl]-1H-pyrazol-3-amine	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
5-methyl-4-(4,5,6-trifluoro-1,3-benzothiazol-2-yl)-1H-pyrazol-3-amine	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
3-N-[3-(dimethylamino)propyl]-4-(5-fluoro-6-methoxy-1,3-benzothiazol-2-yl)-1H-pyrazole-3,5-diamine	IC50	200 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
methyl 2-(3-amino-5-methyl-1H-pyrazol-4-yl)-1,3-benzothiazole-6-carboxylate	IC50	300 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents
2-(3-amino-5-methyl-1H-pyrazol-4-yl)-1,3-benzothiazole-6-carboxamide	IC50	300 nM	US-8754233: Pyrazolylbenzothiazole derivatives and their use as therapeutic agents

ChEMBL bioactivities

319 potent at pChembl≥5 of 327 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.15	IC50	7	nM	CHEMBL3681007
8.00	IC50	10	nM	CHEMBL3681013
8.00	IC50	10	nM	CHEMBL3685712
7.70	IC50	20	nM	CHEMBL3685682
7.70	IC50	20	nM	CHEMBL3685727
7.70	IC50	20	nM	CHEMBL3639798
7.70	Kd	20	nM	NILOTINIB
7.52	IC50	30	nM	CHEMBL3732995
7.50	Kd	32	nM	TELATINIB
7.40	IC50	40	nM	CHEMBL3681027
7.40	IC50	40	nM	CHEMBL3681005
7.40	IC50	40	nM	CHEMBL3685661
7.40	IC50	40	nM	CHEMBL3685652
7.40	IC50	40	nM	CHEMBL3680995
7.30	IC50	50	nM	CHEMBL3685631
7.30	IC50	50	nM	CHEMBL3681008
7.30	IC50	50	nM	CHEMBL3685659
7.22	IC50	60	nM	CHEMBL3681004
7.22	IC50	60	nM	CHEMBL3685693
7.22	IC50	60	nM	CHEMBL3685654
7.22	IC50	60	nM	CHEMBL3680994
7.16	IC50	70	nM	CHEMBL3680998
7.16	IC50	70	nM	CHEMBL3685656
7.16	IC50	70	nM	CHEMBL3680993
7.05	IC50	90	nM	CHEMBL3681024
7.00	IC50	100	nM	CHEMBL3685634
7.00	IC50	100	nM	CHEMBL3685684
7.00	IC50	100	nM	CHEMBL3685688
7.00	IC50	100	nM	CHEMBL3685695
7.00	IC50	100	nM	CHEMBL3685653
7.00	IC50	100	nM	CHEMBL3685713
7.00	IC50	100	nM	CHEMBL3680988
6.89	IC50	130	nM	CHEMBL3681009
6.82	IC50	150	nM	CHEMBL3681006
6.82	IC50	150	nM	CHEMBL3685701
6.72	IC50	190	nM	CHEMBL3685692
6.70	IC50	200	nM	CHEMBL3685635
6.70	IC50	200	nM	CHEMBL3681025
6.70	IC50	200	nM	CHEMBL3681022
6.70	IC50	200	nM	CHEMBL3681014
6.70	IC50	200	nM	CHEMBL3681010
6.70	IC50	200	nM	CHEMBL3685681
6.70	IC50	200	nM	CHEMBL3685673
6.70	IC50	200	nM	CHEMBL3685669
6.70	IC50	200	nM	CHEMBL3685668
6.70	IC50	200	nM	CHEMBL3685664
6.70	IC50	200	nM	CHEMBL3685658
6.70	IC50	200	nM	CHEMBL3685657
6.70	IC50	200	nM	CHEMBL3685715
6.70	IC50	200	nM	CHEMBL3685729

PubChem BioAssay actives

6 with measured affinity, of 305 total; 6 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
Nilotinib	1425024: 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	0.0200	uM
4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-N-methylpyridine-2-carboxamide	1425024: 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	0.0320	uM
N-methyl-3-[1-(4-piperazin-1-ylphenyl)-5-[4-[4-(trifluoromethyl)phenyl]phenyl]pyrazol-3-yl]propanamide	618889: Inhibition of human ILK activity assessed myelin basic protein phosphorylation by radiometric kinase assay in the presence of [gamma 32P]ATP	ic50	0.6000	uM
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine	1425024: 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	1.3290	uM
2,7,8-trimethyl-2-(4-methylpentyl)-3,4-dihydrochromene-6-sulfonamide	1200635: Binding affinity to GST-tagged PH domain of ILK (unknown origin) by surface Plasmon resonance spectroscopy	kd	6.2000	uM
(2R)-2,7,8-trimethyl-2-(4-methylpentyl)-3,4-dihydrochromen-6-ol	1200635: Binding affinity to GST-tagged PH domain of ILK (unknown origin) by surface Plasmon resonance spectroscopy	kd	8.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects binding, affects folding, decreases reaction, decreases expression, increases expression	4
Smoke	decreases expression, increases abundance, increases expression	3
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
bisphenol S	decreases methylation, increases expression	2
bisphenol AF	affects binding, affects folding, decreases reaction, increases expression	2
Aspirin	decreases activity, decreases expression	2
Estradiol	affects binding, increases reaction	2
Rotenone	decreases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
ethyl caffeate	affects expression	1
tamibarotene	increases expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
pyrimidifen	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
pyrachlostrobin	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
picoxystrobin	decreases expression	1
N-methyl-3-(1-(4-(piperazin-1-yl)phenyl)-5-(4’-(trifluoromethyl)-(1,1’-biphenyl)-4-yl)-1H-pyrazol-3-yl)propanamide	decreases expression, decreases reaction, decreases phosphorylation	1
Temozolomide	decreases expression	1
Pioglitazone	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1

ChEMBL screening assays

71 unique, capped per target: 71 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1244364	Binding	Inhibition of ILK	Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. — Leukemia

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AW27	K562 eGFP-ILK	Cancer cell line	Female
CVCL_SS50	HAP1 ILK (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy