ROCK2

Summary

ROCK2 (Rho associated coiled-coil containing protein kinase 2, HGNC:10252) is a protein-coding gene on chromosome 2p25.1, encoding Rho-associated protein kinase 2 (O75116). Protein kinase which is a key regulator of actin cytoskeleton and cell polarity.

The protein encoded by this gene is a serine/threonine kinase that regulates cytokinesis, smooth muscle contraction, the formation of actin stress fibers and focal adhesions, and the activation of the c-fos serum response element. This protein, which is an isozyme of ROCK1 is a target for the small GTPase Rho.

Source: NCBI Gene 9475 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Moderate, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 162 total
• Phenotypes (HPO): 1
• Druggable target: yes — 52 molecules with ChEMBL bioactivity
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_004850

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10252
Approved symbol	ROCK2
Name	Rho associated coiled-coil containing protein kinase 2
Location	2p25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000134318
Ensembl biotype	protein_coding
OMIM	604002
Entrez	9475

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000261535, ENST00000315872, ENST00000401753, ENST00000431087, ENST00000460262, ENST00000462366, ENST00000484951, ENST00000493096, ENST00000697752, ENST00000697790, ENST00000697791, ENST00000697792, ENST00000944889, ENST00000944890, ENST00000944891

RefSeq mRNA: 2 — MANE Select: NM_004850 NM_001321643, NM_004850

CCDS: CCDS42654

Canonical transcript exons

ENST00000315872 — 33 exons

Exon	Start	End
ENSE00000711066	11214357	11214463
ENSE00000913868	11192148	11192361
ENSE00000913869	11192451	11192712
ENSE00000913872	11194955	11195025
ENSE00000913873	11197180	11197348
ENSE00000913874	11197526	11197705
ENSE00000913875	11198491	11198585
ENSE00000913876	11198681	11198774
ENSE00000913877	11200957	11201143
ENSE00000913878	11201310	11201413
ENSE00000913879	11202052	11202121
ENSE00000913880	11207726	11207910
ENSE00000913881	11208287	11208447
ENSE00000913882	11211681	11211840
ENSE00001606097	11235702	11235962
ENSE00001680949	11215321	11215412
ENSE00001747392	11218455	11218466
ENSE00001755280	11224322	11224460
ENSE00001763180	11221198	11221357
ENSE00001798337	11214840	11215086
ENSE00001803971	11222083	11222174
ENSE00002312364	11343996	11344636
ENSE00003507698	11217090	11217169
ENSE00003552905	11194256	11194344
ENSE00003575391	11287655	11287736
ENSE00003592712	11286539	11286639
ENSE00003594475	11249661	11249798
ENSE00003621972	11218966	11219026
ENSE00003644650	11215510	11215645
ENSE00003671086	11227254	11227398
ENSE00003682206	11193779	11193857
ENSE00003682514	11216158	11216206
ENSE00003971699	11179759	11183440

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6579 / max 250.5756, expressed in 1772 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26907	10.6986	1762
26906	0.6524	366
26911	0.4505	96
26910	0.4112	181
26908	0.3278	153
26909	0.0899	30
26905	0.0276	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.39	gold quality
colonic epithelium	UBERON:0000397	96.98	gold quality
middle temporal gyrus	UBERON:0002771	95.40	gold quality
diaphragm	UBERON:0001103	94.59	gold quality
biceps brachii	UBERON:0001507	94.02	gold quality
superficial temporal artery	UBERON:0001614	93.80	gold quality
blood vessel layer	UBERON:0004797	93.76	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.38	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.37	gold quality
cerebellar vermis	UBERON:0004720	93.19	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.86	gold quality
cauda epididymis	UBERON:0004360	92.46	gold quality
rectum	UBERON:0001052	92.10	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.08	gold quality
deltoid	UBERON:0001476	92.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.02	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.02	gold quality
popliteal artery	UBERON:0002250	91.99	gold quality
frontal pole	UBERON:0002795	91.99	gold quality
tibial artery	UBERON:0007610	91.99	gold quality
stromal cell of endometrium	CL:0002255	91.94	gold quality
colonic mucosa	UBERON:0000317	91.92	gold quality
skeletal muscle tissue	UBERON:0001134	91.79	gold quality
artery	UBERON:0001637	91.62	gold quality
smooth muscle tissue	UBERON:0001135	91.58	gold quality
CA1 field of hippocampus	UBERON:0003881	91.53	gold quality
vastus lateralis	UBERON:0001379	91.47	gold quality
urinary bladder	UBERON:0001255	91.42	gold quality
quadriceps femoris	UBERON:0001377	91.39	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.39	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	742.96
E-GEOD-135922	yes	24.35
E-CURD-119	yes	11.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets.

Target	Regulation
ACTA1	Activation
ACTA2	Activation
CCN2	Activation
COL1A1	Activation
FGF2	Activation
FN1	Activation
LPP	Activation
MSN	Activation
NOS3	Repression
NPPA	Activation
TGFB1	Activation

Upstream regulators (CollecTRI, top): HOXD10, PRKDC

miRNA regulators (miRDB)

290 targeting ROCK2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4789-5P	99.98	70.76	2721

Literature-anchored findings (GeneRIF, showing 40)

• Kinetic mechanism for human Rho-Kinase II (ROCK-II). (PMID:12102637)
• ROCK-II-induced membrane blebbing and chromatin condensation require actin cytoskeleton. “ROCK-II” (PMID:12126956)
• characterization and purification of human ROCK-II (PMID:12176052)
• diphosphorylated MRLC and Rho-kinase accumulated and colocalized at the contractile ring and the midbody in dividing cells (PMID:12185584)
• ROKalpha is regulated by CRMP-1 and CRMP2 (PMID:12482610)
• results indicate that remnant-like particles from sudden cardiac death patients upregulate Rho-kinase in coronary vascular smooth muscle cells and markedly enhance coronary vasospastic activity (PMID:15044207)
• Data show that granzyme B directly cleaves ROCK II, and that this causes constitutive kinase activity and bleb formation. (PMID:15699075)
• The crystal structure of an active Rho-kinase fragment containing the kinase domain revealed a head-to-head homodimer through the N-terminal extension forming a helix bundle that structurally integrates the C-terminal extension. (PMID:16531242)
• Common variation in ROCK2 exerts systemic resistance-mediated changes in blood pressure and is novel mechanism for human circulatory control and suggests new possibilities for diagnosis and treatment of subjects at risk of hypertension. (PMID:16585408)
• study investigated the role of RhoA and Rho-kinase in endothelial eNOS protein expression under hypoxic conditions (PMID:16996686)
• These results indicate that 2ME-induced barrier disruption is governed by microtubule depolymerization and p38- and ROCK-dependent mechanisms. (PMID:17012370)
• Dual regulatory role for Rho kinase in fibroblast regulation in which lipid-induced Rho kinase activation suppresses fibroblast morphogenesis while TGF-beta1-induced Rho kinase activation culminates in transformation into myofibroblasts. (PMID:17167780)
• findings report that the Notch1 gene is a p53 target in human keratinocytes with a role in tumor suppression of this cell type through negative regulation of the ROCK1/2 and MRCKalpha kinases (PMID:17344417)
• Plk1 and RhoA function to enhance Rock2 kinase activity in vitro and within cells, and implicate Plk1 as a regulator of multiple pathways that synergistically converge to regulate actomyosin ring contraction during cleavage furrow ingression. (PMID:17446864)
• These findings demonstrate a central role of the GEF-H1/Rho/ROCK-II signaling pathway in the disassembly of apical junctional complex in epithelial cells. (PMID:17596509)
• Inhibition of ROCK activity in human-derived cells enhanced either bacterial adhesion or adhesion and entry in an InlF-independent manner, further suggesting a host species or cell type-specific role for InlF. (PMID:18331468)
• Rock1 and 2 are activated in response to wounding. ROCK activities enhance cell proliferation and epithelial differentiation, but negatively modulate cell migration and adhesion and therefore play a role in regulating corneal epithelial wound healing. (PMID:18495812)
• Rock potently stimulates the differentiation of resting fibroblasts into myofibroblasts and the production of extracellular matrix in scleroderma fibroblasts. (PMID:18668558)
• ROCKI and possibly ROCKII are key factors in regulation of motility/invasion of breast cancer cells (PMID:18695890)
• a feedback loop between Rho/ROCK, Src, and phosphorylated Cav1 in tumor cell protrusions, identifying a novel function for Cav1 in tumor metastasis that may contribute to the poor prognosis of some Cav1-expressing tumors. (PMID:18922892)
• a major haplotype block at the ROCK2 locus is recessively associated with a lower risk of hypertension (PMID:18971541)
• ROCK2 activity and dimerization were dependent upon the interaction between Thr(405) of the hydrophobic motif and Asp(39) of the N-terminal extension. The reciprocal exchange of these residues was permissive for kinase activity, but not for dimerization. (PMID:19099536)
• ROCK1 and ROCK2 regulated myosin light chain phosphatase. ROCK isoforms had distinct and opposing effects on vascular smooth muscle cell (VSMC) morphology and ROCK2, but not ROCK1, had a predominant role in VSMC contractility. (PMID:19131646)
• Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven retinal neovascularization and sprouting angiogenesis. (PMID:19181962)
• overexpressed in hepatocellular carcinoma and played a significant role in regulating cytoskeletal events and contributed to the invasion of hepatocellular carcinoma (PMID:19205033)
• Stimulation of PKC disrupts epithelial apical junctions via ROCK-II dependent stimulation of actomyosin contractility. (PMID:19422706)
• Data conclude that common genetic variation in ROCK2 is unlikely to make a major contribution to the risk of pre-eclampsia, but cannot exclude the possibility of having missed non-coding functional variants or rare coding variants. (PMID:19435756)
• Provide evidence for Rho-kinase activation in patients with pulmonary arterial hypertension. (PMID:19590140)
• These data suggest that ROCK1 and ROCK2 play distinct roles in regulating keratinocyte adhesion and terminal differentiation. (PMID:19997641)
• Pharmacologic inhibition of Rho kinase 2 signaling blocked LPA-induced p65 phosphorylation and suppressed ICAM-1 and VCAM-1 expression. (PMID:20164172)
• A functional proteomics approach enabled the authors to identify novel LOX-1 interactors that potentially contribute to the cellular and signaling functions of LOX-1. (PMID:20181930)
• results suggest that miR-138 plays an important role in TSCC cell migration and invasion by concurrently targeting RhoC and ROCK2, and miR-138 may serve as a novel therapeutic target for TSCC patients at risk of metastatic disease (PMID:20232393)
• Results suggest that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. (PMID:20429915)
• upregulated rho-associated protein kinase 2, p-cofilin and intracellular adhesion molecule-1, and downregulated E-cadherin were found in esophageal squamous cell cancer cells (PMID:20504226)
• Thr431Asn polymorphism of the ROCK2 gene could be a risk factor for the metastases of the breast cancer, and may help in predicting the prognosis. (PMID:20939434)
• Expression of miR-139 is reduced in human metastatic hepatocellular carcinoma samples and correlates with prognosis. The microRNA miR-139 interacts with ROCK2 and reduces its expression in hepatocellular carcinoma. (PMID:20951699)
• The results of this study suggested that there were no evidence for an association of ROCK2 gene Thr431Asn and Arg83Lys polymorphisms with diabetes or diabetic retinopathy in the Turkish population. (PMID:20961215)
• results suggested that a complex consisting of BRCA2, NPM, and ROCK2 maintains the numerical integrity of centrosomes and accurate cell division and that dysfunction of this regulation might be involved in the tumorigenesis of breast cancer (PMID:21084279)
• LR11 is phosphorylated in vivo and indicate that ROCK2 phosphorylation of LR11 may enhance LR11 mediated processing of APP and amyloid production. (PMID:21147781)
• Ras/Raf/MAPK and RhoA/ROCKII signalling pathways are abnormally activated in eutopic endometrial stromal cells of patients with endometriosis (PMID:21303778)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	rock2b	ENSDARG00000004877
danio_rerio	rock2a	ENSDARG00000017500
danio_rerio	si:dkey-65b13.11	ENSDARG00000096433
danio_rerio	rock2bl	ENSDARG00000100381
danio_rerio	si:dkey-65b13.9	ENSDARG00000105249
mus_musculus	Rock2	ENSMUSG00000020580
rattus_norvegicus	Rock2	ENSRNOG00000004496
drosophila_melanogaster	Rok	FBGN0026181
caenorhabditis_elegans	let-502	WBGENE00002694

Paralogs (5): ROCK1 (ENSG00000067900), CIT (ENSG00000122966), CDC42BPA (ENSG00000143776), CDC42BPG (ENSG00000171219), CDC42BPB (ENSG00000198752)

Protein

Protein identifiers

Rho-associated protein kinase 2 — O75116 (reviewed: O75116)

Alternative names: Rho kinase 2, Rho-associated, coiled-coil-containing protein kinase 2, Rho-associated, coiled-coil-containing protein kinase II, p164 ROCK-2

All UniProt accessions (7): A0A2P9DU05, A0A8V8TL82, A0A8V8TL90, C9JFJ0, O75116, D6REE7, E9PF63

UniProt curated annotations — full annotation on UniProt →

Function. Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation.

Subunit / interactions. Homodimer. Interacts with IRS1. Interacts with RAF1. Interacts with RHOA (activated by GTP), RHOB and RHOC. Interacts with PPP1R12A. Interacts with EP300. Interacts with CHORDC1. Interacts with BRCA2. Interacts with NPM1; this interaction enhances ROCK2 activity. Interacts with SORL1. Interacts with PJVK.

Subcellular location. Cytoplasm. Cell membrane. Nucleus. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Expressed in the brain (at protein level).

Post-translational modifications. Phosphorylation at Tyr-722 reduces its binding to RHOA and is crucial for focal adhesion dynamics. Dephosphorylation by PTPN11 stimulates its RHOA binding activity. Cleaved by granzyme B during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing.

Activity regulation. Activated by RHOA binding. Inhibited by Y-27632.

Domain organisation. An interaction between Thr-414 and Asp-48 is essential for kinase activity and dimerization.

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

RefSeq proteins (2): NP_001308572, NP_004841* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR001849	PH_domain	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011072	HR1_rho-bd	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015008	ROCK_Rho-bd_dom	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020684	ROCK1/ROCK2	Family
IPR029878	ROCK2_cat	Domain
IPR037311	ROCK2_HR1	Domain
IPR046349	C1-like_sf	Homologous_superfamily
IPR050839	Rho-assoc_Ser/Thr_Kinase	Family
IPR057529	MRCK/ROCK_PH	Domain

Pfam: PF00069, PF08912, PF25346

Catalyzed reactions (Rhea), 2 shown:

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

UniProt features (70 total): helix 22, strand 12, modified residue 6, domain 5, region of interest 5, turn 5, sequence variant 4, coiled-coil region 2, binding site 2, chain 1, compositionally biased region 1, active site 1, site 1, mutagenesis site 1, sequence conflict 1, zinc finger region 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
8X92	X-RAY DIFFRACTION	2.2
7JNT	X-RAY DIFFRACTION	2.21
7JOV	X-RAY DIFFRACTION	2.59
8X8X	X-RAY DIFFRACTION	2.6
9EP8	X-RAY DIFFRACTION	2.63
6P5M	X-RAY DIFFRACTION	2.65
8X8Z	X-RAY DIFFRACTION	2.7
8GDS	X-RAY DIFFRACTION	2.71
7P6O	X-RAY DIFFRACTION	2.75
4L6Q	X-RAY DIFFRACTION	2.79
7P6P	X-RAY DIFFRACTION	2.82
6ED6	X-RAY DIFFRACTION	2.86
7P6Q	X-RAY DIFFRACTION	2.89
9HFP	X-RAY DIFFRACTION	2.92
4WOT	X-RAY DIFFRACTION	2.93
7P6N	X-RAY DIFFRACTION	3
9JCU	X-RAY DIFFRACTION	3.02
5U7Q	X-RAY DIFFRACTION	3.15
8X8Y	X-RAY DIFFRACTION	3.2
6P5P	X-RAY DIFFRACTION	3.3
5U7R	X-RAY DIFFRACTION	3.33

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75116-F1	76.79	0.26

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 (2): 214 (proton acceptor); 1131–1132 (cleavage; by granzyme b)

Ligand- & substrate-binding residues (2): 98–106; 121

Post-translational modifications (6): 414, 722, 1137, 1212, 1362, 1374

Mutagenesis-validated functional residues (1):

Position	Phenotype
1131	abolishes cleavage by granzyme b.

Function

Pathways and Gene Ontology

Reactome pathways

32 pathways

ID	Pathway
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-3928663	EPHA-mediated growth cone collapse
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-416572	Sema4D induced cell migration and growth-cone collapse
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-5627117	RHO GTPases Activate ROCKs
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013407	RHOH GTPase cycle
R-HSA-9013422	RHOBTB1 GTPase cycle
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-194138	Signaling by VEGF
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-372790	Signaling by GPCR
R-HSA-373755	Semaphorin interactions
R-HSA-388396	GPCR downstream signalling
R-HSA-400685	Sema4D in semaphorin signaling
R-HSA-422475	Axon guidance
R-HSA-5663205	Infectious disease
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9675108	Nervous system development
R-HSA-9679506	SARS-CoV Infections
R-HSA-9706574	RHOBTB GTPase Cycle

MSigDB gene sets: 566 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_MITOTIC_CYTOKINESIS, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, chr2p25, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_POSITIVE_REGULATION_OF_AMIDE_METABOLIC_PROCESS

GO Biological Process (55): mitotic cytokinesis (GO:0000281), epithelial to mesenchymal transition (GO:0001837), response to ischemia (GO:0002931), aortic valve morphogenesis (GO:0003180), protein phosphorylation (GO:0006468), smooth muscle contraction (GO:0006939), Rho protein signal transduction (GO:0007266), positive regulation of cardiac muscle hypertrophy (GO:0010613), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of centrosome duplication (GO:0010825), negative regulation of angiogenesis (GO:0016525), actin cytoskeleton organization (GO:0030036), regulation of cell adhesion (GO:0030155), positive regulation of cell migration (GO:0030335), cortical actin cytoskeleton organization (GO:0030866), actomyosin structure organization (GO:0031032), regulation of nervous system process (GO:0031644), positive regulation of connective tissue growth factor production (GO:0032723), regulation of actin cytoskeleton organization (GO:0032956), regulation of circadian rhythm (GO:0042752), positive regulation of MAPK cascade (GO:0043410), host-mediated perturbation of viral process (GO:0044788), negative regulation of nitric oxide biosynthetic process (GO:0045019), regulation of keratinocyte differentiation (GO:0045616), rhythmic process (GO:0048511), embryonic morphogenesis (GO:0048598), centrosome duplication (GO:0051298), regulation of stress fiber assembly (GO:0051492), positive regulation of stress fiber assembly (GO:0051496), regulation of focal adhesion assembly (GO:0051893), mRNA destabilization (GO:0061157), negative regulation of biomineral tissue development (GO:0070168), response to transforming growth factor beta (GO:0071559), protein localization to plasma membrane (GO:0072659), positive regulation of fibroblast growth factor production (GO:0090271), blood vessel diameter maintenance (GO:0097746), regulation of angiotensin-activated signaling pathway (GO:0110061), negative regulation of protein localization to lysosome (GO:0150033), regulation of cellular response to hypoxia (GO:1900037)

GO Molecular Function (18): protease binding (GO:0002020), RNA binding (GO:0003723), protein serine/threonine kinase activity (GO:0004674), structural molecule activity (GO:0005198), ATP binding (GO:0005524), zinc ion binding (GO:0008270), small GTPase binding (GO:0031267), tau protein binding (GO:0048156), tau-protein kinase activity (GO:0050321), endopeptidase activator activity (GO:0061133), Rho-dependent protein serine/threonine kinase activity (GO:0072518), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (9): nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cytoplasmic ribonucleoprotein granule (GO:0036464), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
RHO GTPase cycle	4
EPH-Ephrin signaling	2
GPCR downstream signalling	1
Sema4D in semaphorin signaling	1
Signaling by VEGF	1
RHO GTPase Effectors	1
RHOBTB GTPase Cycle	1
SARS-CoV Infections	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Axon guidance	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
actin cytoskeleton organization	3
gene expression	2
regulation of gene expression	2
protein kinase activity	2
protein serine/threonine kinase activity	2
cytoplasm	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
mesenchymal cell differentiation	1
response to stress	1
aortic valve development	1
heart valve morphogenesis	1
phosphorylation	1
protein modification process	1
muscle contraction	1
small GTPase-mediated signal transduction	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
positive regulation of muscle hypertrophy	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
regulation of centrosome duplication	1
centrosome duplication	1
positive regulation of cell cycle process	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
cytoskeleton organization	1
actin filament-based process	1
cell adhesion	1
regulation of cellular process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
cortical cytoskeleton organization	1
regulation of system process	1
nervous system process	1
positive regulation of cytokine production	1

Protein interactions and networks

STRING

3813 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ROCK2	RHOA	P06749	974
ROCK2	A0A087WZG4	A0A087WZG4	865
ROCK2	ARHGEF18	Q6ZSZ5	865
ROCK2	MYL2	P10916	791
ROCK2	NPM1	P06748	784
ROCK2	CFL2	Q9Y281	754
ROCK2	CFL1	P23528	753
ROCK2	PDCD10	Q9BUL8	707
ROCK2	PPP1R12A	O14974	701
ROCK2	KRIT1	O00522	688
ROCK2	MSN	P26038	683
ROCK2	RND3	P52199	678
ROCK2	BRCA2	P51587	673
ROCK2	CGN	Q9P2M7	662
ROCK2	CCM2	Q9BSQ5	640

IntAct

106 interactions, top by confidence:

A	B	Type	Score
NFKBIA	CHUK	psi-mi:“MI:0217”(phosphorylation reaction)	0.950
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RPS6KA3	ROCK2	psi-mi:“MI:0914”(association)	0.640
PFDN1	PFDN6	psi-mi:“MI:0914”(association)	0.640
ROCK2	APP	psi-mi:“MI:0915”(physical association)	0.560
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
LRPAP1	LRP4	psi-mi:“MI:0914”(association)	0.530
PDPK1	AGRN	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
POLR1C	POLR3A	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
LURAP1	TRIM24	psi-mi:“MI:0914”(association)	0.530
ROCK2	STAT3	psi-mi:“MI:0915”(physical association)	0.520
PPP1R14B	ROCK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
STAU1	DYNC1I1	psi-mi:“MI:0914”(association)	0.430
ROCK2	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
ROCK2	HNRNPCL2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (202): ROCK2 (Affinity Capture-MS), RACGAP1 (Co-fractionation), ROCK2 (Affinity Capture-MS), ROCK2 (Affinity Capture-MS), ROCK2 (Affinity Capture-MS), ROCK2 (Affinity Capture-MS), ROCK2 (Affinity Capture-Western), ROCK2 (Reconstituted Complex), ROCK2 (Co-localization), POLR1C (Affinity Capture-MS), ROCK1 (Affinity Capture-MS), DNAJB11 (Affinity Capture-MS), FBXO42 (Affinity Capture-MS), ROCK2 (Affinity Capture-MS), ROCK2 (Affinity Capture-MS)

ESM2 similar proteins: A1Z8P9, A3KGV1, B6MFW3, F1MA98, F6ZDS4, G5E861, M3TYT0, O01583, O15078, O54874, O75116, O77819, P12270, P61584, P70335, P70336, P85001, P85120, Q02224, Q13464, Q28021, Q3UU96, Q3V6T2, Q4R6W3, Q5BJF6, Q5SNZ0, Q5TZ80, Q5VT25, Q5ZJ27, Q5ZKK5, Q62868, Q63644, Q66GS9, Q69ZB0, Q6A078, Q6AYX5, Q6NRB0, Q6NRC9, Q6NRW2, Q6NY15

Diamond homologs: A0A7J6K7I9, A0A7J6K7Y0, A0A7J6KD88, A8X775, B1WAR9, C4YRB7, D2HXI8, E1C2I2, E9PSL7, G1X456, G5EGQ3, M3TYT0, O00506, O01583, O01700, O14578, O54874, O61267, O75116, O77819, O80902, O88643, O97627, P05131, P0CY23, P0CY24, P13677, P21146, P25098, P26817, P26818, P32865, P34100, P35465, P38070, P48562, P49025, P49673, P54265, P70335

SIGNOR signaling

24 interactions.

A	Effect	B	Mechanism
ROCK2	down-regulates	SH3GL2	phosphorylation
ROCK2	up-regulates	IRF4	phosphorylation
ROCK2	“up-regulates quantity by expression”	LPP	“transcriptional regulation”
Y-27632	down-regulates	ROCK2	“chemical inhibition”
ROCK2	“up-regulates activity”	MYL9	phosphorylation
GEM	“down-regulates activity”	ROCK2	binding
ROCK2	up-regulates	Actin_cytoskeleton_reorganization
N-(6-fluoro-1H-indazol-5-yl)-6-methyl-2-oxo-4-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-pyridine-5-carboxamide	“down-regulates activity”	ROCK2	“chemical inhibition”
ROCK2	“up-regulates activity”	MYL12B	phosphorylation
ROCK2	“up-regulates activity”	EP300	phosphorylation
ROCK2	“up-regulates quantity”	APP	phosphorylation
ROCK2	“up-regulates activity”	LHX3	phosphorylation
ROCK2	up-regulates	DPYSL2	phosphorylation
ROCK2	“up-regulates activity”	PPP1R14A	phosphorylation
ROCK2	“down-regulates activity”	PPP1R12A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 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
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	6	11.7×	2e-03
Signaling by BRAF and RAF1 fusions	5	11.4×	9e-03
Interleukin-4 and Interleukin-13 signaling	7	9.6×	2e-03
Signaling by Interleukins	10	8.6×	2e-04
Diseases of signal transduction by growth factor receptors and second messengers	8	6.1×	7e-03
Cytokine Signaling in Immune system	11	6.0×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein autophosphorylation	6	9.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	103
Likely benign	9
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

5697 predictions. Top by Δscore:

Variant	Effect	Δscore
2:11183436:GTTAG:G	acceptor_gain	1.0000
2:11183437:TTAG:T	acceptor_gain	1.0000
2:11183438:TAG:T	acceptor_gain	1.0000
2:11183438:TAGCT:T	acceptor_loss	1.0000
2:11183441:CTGA:C	acceptor_loss	1.0000
2:11192357:ATATA:A	acceptor_gain	1.0000
2:11192358:TATA:T	acceptor_gain	1.0000
2:11192359:ATA:A	acceptor_gain	1.0000
2:11192360:TA:T	acceptor_gain	1.0000
2:11192362:C:CC	acceptor_gain	1.0000
2:11192446:TTTAC:T	donor_loss	1.0000
2:11192447:TTACC:T	donor_loss	1.0000
2:11192448:TACC:T	donor_loss	1.0000
2:11192449:A:AG	donor_loss	1.0000
2:11192450:C:CA	donor_loss	1.0000
2:11192617:ATGTC:A	donor_gain	1.0000
2:11192709:GAAT:G	acceptor_gain	1.0000
2:11192711:AT:A	acceptor_gain	1.0000
2:11192712:TC:T	acceptor_loss	1.0000
2:11192713:C:CA	acceptor_loss	1.0000
2:11192713:C:CC	acceptor_gain	1.0000
2:11192715:A:C	acceptor_gain	1.0000
2:11193854:CTTG:C	acceptor_gain	1.0000
2:11193858:C:CC	acceptor_gain	1.0000
2:11194248:ACACT:A	donor_loss	1.0000
2:11194249:CACT:C	donor_loss	1.0000
2:11194250:ACTTA:A	donor_loss	1.0000
2:11194251:CTTAC:C	donor_loss	1.0000
2:11194252:TTA:T	donor_loss	1.0000
2:11194253:T:TC	donor_loss	1.0000

AlphaMissense

9274 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:11192293:A:G	W1340R	1.000
2:11192293:A:T	W1340R	1.000
2:11192331:A:G	L1327P	1.000
2:11192455:G:C	C1315W	1.000
2:11192456:C:A	C1315F	1.000
2:11192456:C:G	C1315S	1.000
2:11192456:C:T	C1315Y	1.000
2:11192457:A:G	C1315R	1.000
2:11192457:A:T	C1315S	1.000
2:11192499:G:C	H1301D	1.000
2:11192512:G:C	C1296W	1.000
2:11192513:C:A	C1296F	1.000
2:11192513:C:G	C1296S	1.000
2:11192513:C:T	C1296Y	1.000
2:11192514:A:G	C1296R	1.000
2:11192514:A:T	C1296S	1.000
2:11192521:G:C	C1293W	1.000
2:11192522:C:A	C1293F	1.000
2:11192522:C:G	C1293S	1.000
2:11192522:C:T	C1293Y	1.000
2:11192523:A:G	C1293R	1.000
2:11192523:A:T	C1293S	1.000
2:11192531:G:T	A1290D	1.000
2:11192556:A:G	W1282R	1.000
2:11192556:A:T	W1282R	1.000
2:11192558:A:G	L1281P	1.000
2:11192569:A:C	C1277W	1.000
2:11192570:C:A	C1277F	1.000
2:11192570:C:T	C1277Y	1.000
2:11192571:A:G	C1277R	1.000

dbSNP variants (sampled 300 via entrez): RS1000008515 (2:11263560 A>G), RS1000009014 (2:11312829 C>T), RS1000045608 (2:11343109 G>T), RS1000101991 (2:11313014 A>G), RS1000158226 (2:11239874 C>T), RS1000164743 (2:11301822 G>A), RS1000169542 (2:11197122 A>T), RS1000198274 (2:11342407 T>A), RS1000221091 (2:11294380 T>A), RS1000262810 (2:11288038 G>C), RS1000290908 (2:11227519 C>G,T), RS1000316325 (2:11339819 G>A), RS1000324564 (2:11189391 T>C), RS1000352439 (2:11288367 T>C), RS1000360561 (2:11294875 C>T)

Disease associations

OMIM: gene MIM:604002 | disease phenotypes: MIM:236750

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Mondo (3): non-immune hydrops fetalis (MONDO:0009369), dextrocardia (MONDO:0015661), congenital heart disease (MONDO:0005453)

Orphanet (2): Non-immune hydrops fetalis (Orphanet:363999), Dextrocardia (Orphanet:1666)

HPO phenotypes

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

HPO	Term
HP:0001651	Dextrocardia

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST010245_48	LDL cholesterol levels	4.000000e-08
GCST90000025_794	Appendicular lean mass	1.000000e-11
GCST90002388_61	Lymphocyte count	9.000000e-13
GCST90002397_764	Mean spheric corpuscular volume	6.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003914	Dextrocardia	C14.240.400.280; C14.280.400.280; C16.131.240.400.280; C16.131.810.250
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111459 (PROTEIN FAMILY), CHEMBL2973 (SINGLE PROTEIN), CHEMBL4523649 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

52 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 239,293 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL2005186	BELUMOSUDIL	4	1,817
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3622821	UPADACITINIB	4	2,726
CHEMBL4594250	NETARSUDIL	4	1,025
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL38380	FASUDIL	3	11,953
CHEMBL2219422	AFURESERTIB	3	1,467
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3426621	RIPASUDIL	3
CHEMBL428690	ALVOCIDIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL541388	FASUDIL HYDROCHLORIDE	2
CHEMBL1088751	PH-797804	2
CHEMBL1230609	FORETINIB	2
CHEMBL1667969	SAR-407899 FREE BASE	2
CHEMBL1721885	SU-014813	2
CHEMBL1944698	ZOTIRACICLIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Rho kinase

Most potent curated ligand interactions (20 total), top 20:

Ligand	Action	Affinity	Parameter
compound 8 [PMID: 25898023]	Inhibition	9.0	pIC50
RKI-1447	Inhibition	9.0	pIC50
compound 11d [DOI: 10.1039/c0md00194e]	Inhibition	9.0	pIC50
compound 35 [PMID: 20684608]	Inhibition	9.0	pIC50
compound 23 [PMID: 35816678]	Inhibition	8.52	pIC50
GSK269962A	Inhibition	8.4	pIC50
compound 32 [PMID: 20471253]	Inhibition	8.4	pIC50
sovesudil	Inhibition	8.29	pIC50
ROCK inhibitor 3	Inhibition	8.11	pIC50
HSD1590	Inhibition	7.95	pKd
netarsudil	Inhibition	7.95	pIC50
Rho kinase inhibitor IV	Inhibition	7.93	pIC50
ripasudil	Inhibition	7.72	pIC50
compound 22 [PMID: 20462760]	Inhibition	7.72	pIC50
SAR407899	Inhibition	6.99	pIC50
belumosudil	Inhibition	6.98	pIC50
ninvosudil	Inhibition	6.94	pKi
cortistatin A	Inhibition	6.66	pKd
zelasudil	Inhibition	6.52	pIC50
fasudil	Inhibition	5.89	pIC50

Binding affinities (BindingDB)

2544 measured of 3190 human assays (3216 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[(6S)-6-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]-3-[[[3-(1H-pyrazol-4-yl)benzoyl]amino]methyl]benzamide	IC50	0.16 nM	US-8697911: Rho kinase inhibitors
N-[[3-[(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)carbamoyl]phenyl]methyl]-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide	IC50	0.17 nM	US-8697911: Rho kinase inhibitors
N-[[3-[(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)carbamoyl]phenyl]methyl]-5-pyridin-4-ylthiophene-2-carboxamide	IC50	0.18 nM	US-8697911: Rho kinase inhibitors
6-ethyl-N-[(1R)-1-(3- methoxyphenyl)ethyl]- 6H-isochromeno[3,4-c] pyridine-8-carboxamide	IC50	0.18 nM	US-9914740: Tricyclic pyrido-carboxamide derivatives as rock inhibitors
N-(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)-3-[[(4-pyridin-4-ylbenzoyl)amino]methyl]benzamide	IC50	0.195 nM	US-8697911: Rho kinase inhibitors
N-[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]-3-[[[4-(1,3-oxazol-5-yl)benzoyl]amino]methyl]benzamide	IC50	0.2 nM	US-8697911: Rho kinase inhibitors
N-[[3-[[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3-pyridin-4-yl-1H-pyrazole-5-carboxamide	IC50	0.2 nM	US-8697911: Rho kinase inhibitors
2-[2-(dimethylamino)ethoxy]-5-fluoro-4-(3-methylpyrazolidin-4-yl)-N-[(1R)-1-phenylethyl]benzamide	IC50	0.2 nM	US-9458110: Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
N-(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)-3-[[[4-(1,3-oxazol-5-yl)benzoyl]amino]methyl]benzamide	IC50	0.21 nM	US-8697911: Rho kinase inhibitors
1-(4-amino-1,2,5-oxadiazol-3-yl)-N-[[3-[[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-5-phenyltriazole-4-carboxamide	IC50	0.21 nM	US-8697911: Rho kinase inhibitors
N-[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]-3-[[(4-pyridin-4-ylbenzoyl)amino]methyl]benzamide	IC50	0.22 nM	US-8697911: Rho kinase inhibitors
N-[[3-[(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)carbamoyl]phenyl]methyl]-3-pyridin-4-yl-1H-pyrazole-5-carboxamide	IC50	0.22 nM	US-8697911: Rho kinase inhibitors
N-[[3-[[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide	IC50	0.22 nM	US-8697911: Rho kinase inhibitors
N-[[3-[(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)carbamoyl]phenyl]methyl]-3-pyridin-4-yl-1H-pyrazole-5-carboxamide	IC50	0.23 nM	US-8697911: Rho kinase inhibitors
N-[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]-3-[[(4-imidazol-1-ylbenzoyl)amino]methyl]benzamide	IC50	0.24 nM	US-8697911: Rho kinase inhibitors
N-[[3-[(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)carbamoyl]phenyl]methyl]-5-pyridin-4-ylthiophene-2-carboxamide	IC50	0.25 nM	US-8697911: Rho kinase inhibitors
N-[[3-[[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-4-methyl-2-pyridin-4-yl-1,3-thiazole-5-carboxamide	IC50	0.25 nM	US-8697911: Rho kinase inhibitors
N-[(1S)-1-[3-(cyclopentylcarbamoyl)phenyl]-2-hydroxyethyl]-2-ethoxy-4-(1H-pyrazol-4-yl)benzamide	IC50	0.25 nM	US-10738007: Amide compounds as kinase inhibitors, compositions and methods of treatment
N-(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)-3-[[(4-pyridin-4-ylbenzoyl)amino]methyl]benzamide	IC50	0.26 nM	US-8697911: Rho kinase inhibitors
1-methyl-2-N-[[3-[(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)carbamoyl]phenyl]methyl]indole-2,6-dicarboxamide	IC50	0.26 nM	US-8697911: Rho kinase inhibitors
3-methoxy-4-pyrazolidin-4-yl-N-[[3-(4,5,6,7-tetrahydro-[1,3]thiazolo[5,4-c]pyridin-2-ylcarbamoyl)phenyl]methyl]benzamide	IC50	0.26 nM	US-9458110: Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
7-cyano-N-[[3-[[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]imidazo[1,2-a]pyridine-2-carboxamide	IC50	0.27 nM	US-8697911: Rho kinase inhibitors
N-[[3-[[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-5-pyridin-4-ylthiophene-2-carboxamide	IC50	0.27 nM	US-8697911: Rho kinase inhibitors
3,4-dimethoxy-N-[(1R)-1-[3-[[(6S)-6-(propylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]ethyl]benzamide	IC50	0.3 nM	US-9079880: Rho kinase inhibitors
(2R)-N-(3-cyanophenyl)-2-[3-[[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]pyrrolidine-1-carboxamide	IC50	0.3 nM	US-9079880: Rho kinase inhibitors
N-[[3-[[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-2-pyridin-3-yl-1,3-thiazole-4-carboxamide	IC50	0.32 nM	US-8697911: Rho kinase inhibitors
N-[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]-3-[[[3-(1H-pyrazol-4-yl)benzoyl]amino]methyl]benzamide	IC50	0.32 nM	US-8697911: Rho kinase inhibitors
1-(4-amino-1,2,5-oxadiazol-3-yl)-N-[[3-[[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-5-methyltriazole-4-carboxamide	IC50	0.33 nM	US-8697911: Rho kinase inhibitors
N-[[3-[[(6S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-3-pyridin-4-yl-1H-pyrazole-5-carboxamide	IC50	0.34 nM	US-8697911: Rho kinase inhibitors
methyl 3-[[(6-methyl-6H-isochromeno[3,4-c]pyridin-8-yl)methylamino]methyl]benzoate	IC50	0.34 nM	US-9914740: Tricyclic pyrido-carboxamide derivatives as rock inhibitors
3-[[[4-(5-methyltetrazol-1-yl)benzoyl]amino]methyl]-N-[(6S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]benzamide	IC50	0.35 nM	US-8697911: Rho kinase inhibitors
N-[(1R)-1-(3-methoxyphenyl)ethyl]-6H-isochromeno[4,3-b]pyridine-8-carboxamide	IC50	0.35 nM	US-9914740: Tricyclic pyrido-carboxamide derivatives as rock inhibitors
N-[[3-[[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-5-(1,3-oxazol-5-yl)thiophene-2-carboxamide	IC50	0.37 nM	US-8697911: Rho kinase inhibitors
4-methyl-N-[[3-[[(6S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]-2-pyridin-4-yl-1,3-thiazole-5-carboxamide	IC50	0.37 nM	US-8697911: Rho kinase inhibitors
3-[[(4-imidazol-1-ylbenzoyl)amino]methyl]-N-[(6S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]benzamide	IC50	0.38 nM	US-8697911: Rho kinase inhibitors
6-hydroxy-N-[[3-[(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)carbamoyl]phenyl]methyl]naphthalene-2-carboxamide	IC50	0.39 nM	US-8697911: Rho kinase inhibitors
(2R)-2-[3-[[(6S)-6-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]-N-(3-cyanophenyl)pyrrolidine-1-carboxamide	IC50	0.39 nM	US-9079880: Rho kinase inhibitors
3-methoxy-N-[[3-[(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)carbamoyl]phenyl]methyl]-4-pyrazolidin-4-ylbenzamide	IC50	0.39 nM	US-9458110: Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
4-methoxy-3-methyl-N-[(1R)-1-[3-[[(6S)-6-(propylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]ethyl]benzamide	IC50	0.4 nM	US-9079880: Rho kinase inhibitors
N-[(6S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]-3-[[[3-(1H-pyrazol-4-yl)benzoyl]amino]methyl]benzamide	IC50	0.41 nM	US-8697911: Rho kinase inhibitors
N-[(6S)-6-(dimethylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]-3-[[[4-(5-methyltetrazol-1-yl)benzoyl]amino]methyl]benzamide	IC50	0.43 nM	US-8697911: Rho kinase inhibitors
N-[(6S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]-3-[[[4-(1,3-oxazol-5-yl)benzoyl]amino]methyl]benzamide	IC50	0.43 nM	US-8697911: Rho kinase inhibitors
3-methoxy-N-[[3-[(1-methylpiperidin-4-yl)carbamoyl]phenyl]methyl]-4-pyrazolidin-4-ylbenzamide	IC50	0.43 nM	US-9458110: Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
N-[(6R)-6-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]-3-[[[3-(1H-pyrazol-4-yl)benzoyl]amino]methyl]benzamide	IC50	0.45 nM	US-8697911: Rho kinase inhibitors
2-N-[[3-[(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)carbamoyl]phenyl]methyl]-1H-indole-2,6-dicarboxamide	IC50	0.45 nM	US-8697911: Rho kinase inhibitors
N-[[3-[(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)carbamoyl]phenyl]methyl]-5-(1,3-oxazol-5-yl)thiophene-2-carboxamide	IC50	0.45 nM	US-8697911: Rho kinase inhibitors
3-chloro-4-methoxy-N-[(1R)-1-[3-[[(6S)-6-(propylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]ethyl]benzamide	IC50	0.5 nM	US-9079880: Rho kinase inhibitors
N-[(1R)-1-(3-methoxyphenyl)ethyl]-5H-chromeno[3,4-c]pyridine-8-carboxamide	IC50	0.51 nM	US-9914740: Tricyclic pyrido-carboxamide derivatives as rock inhibitors
7-cyano-N-[[3-[[(6S)-6-morpholin-4-yl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl]carbamoyl]phenyl]methyl]imidazo[1,2-a]pyridine-2-carboxamide	IC50	0.52 nM	US-8697911: Rho kinase inhibitors
N-(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)-3-[[[3-(1H-pyrazol-4-yl)benzoyl]amino]methyl]benzamide	IC50	0.53 nM	US-8697911: Rho kinase inhibitors

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.77	IC50	0.017	nM	CHEMBL3666733
10.70	Kd	0.02	nM	CHEMBL2023843
10.68	Kd	0.021	nM	CHEMBL525385
10.64	IC50	0.023	nM	CHEMBL3666753
10.44	IC50	0.036	nM	CHEMBL3666735
10.31	IC50	0.049	nM	CHEMBL3666738
10.00	IC50	0.1	nM	CHEMBL5864025
9.89	Ki	0.13	nM	CHEMBL6175959
9.82	Ki	0.15	nM	CHEMBL6169753
9.80	IC50	0.16	nM	CHEMBL3680709
9.77	IC50	0.17	nM	CHEMBL3680738
9.74	IC50	0.18	nM	CHEMBL3578252
9.74	IC50	0.18	nM	CHEMBL3680755
9.74	IC50	0.18	nM	CHEMBL5287722
9.72	IC50	0.19	nM	CHEMBL3949136
9.71	IC50	0.195	nM	CHEMBL3680767
9.70	Ki	0.2	nM	CHEMBL3792888
9.70	IC50	0.2	nM	CHEMBL3680772
9.70	IC50	0.2	nM	CHEMBL3680805
9.70	Ki	0.2	nM	NETARSUDIL-M1
9.70	IC50	0.2	nM	CHEMBL5397091
9.70	IC50	0.2	nM	CHEMBL5414146
9.70	Ki	0.2	nM	CHEMBL6161530
9.68	IC50	0.21	nM	CHEMBL3680698
9.68	IC50	0.21	nM	CHEMBL3680773
9.68	IC50	0.21	nM	CHEMBL4763198
9.66	IC50	0.22	nM	CHEMBL3680752
9.66	IC50	0.22	nM	CHEMBL3680759
9.66	IC50	0.22	nM	CHEMBL3680768
9.64	IC50	0.23	nM	CHEMBL3680736
9.64	IC50	0.23	nM	CHEMBL3902471
9.64	IC50	0.23	nM	CHEMBL5991229
9.62	IC50	0.24	nM	CHEMBL3680771
9.62	Kd	0.24	nM	STAUROSPORINE
9.61	IC50	0.246	nM	STAUROSPORINE
9.60	IC50	0.25	nM	CHEMBL3680735
9.60	IC50	0.25	nM	CHEMBL3680804
9.60	IC50	0.25	nM	CHEMBL6055719
9.59	IC50	0.26	nM	CHEMBL3680728
9.59	IC50	0.26	nM	CHEMBL3680740
9.57	IC50	0.27	nM	CHEMBL3680748
9.57	IC50	0.27	nM	CHEMBL3680765
9.55	IC50	0.28	nM	CHEMBL4114628
9.52	IC50	0.3	nM	CHEMBL3700926
9.52	IC50	0.3	nM	CHEMBL3700932
9.52	IC50	0.3	nM	CHEMBL3968772
9.52	IC50	0.3	nM	CHEMBL3913336
9.52	IC50	0.3	nM	CHEMBL4114628
9.52	IC50	0.3	nM	CHEMBL5753142
9.52	IC50	0.3	nM	CHEMBL5776277

PubChem BioAssay actives

1967 with measured affinity, of 4745 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
(2S,3S,4R,5R)-N-[6-[[(2R)-6-amino-1-[[6-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxohexan-2-yl]amino]-6-oxohexyl]-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide	659402: Displacement of fluorescent-ARC-1063 from His6-tagged recombinant human ROCK2 by luminescence intensity assay	kd	<0.0001	uM
N-[6-[[(2R)-6-amino-1-[[6-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxohexan-2-yl]amino]-6-oxohexyl]-5-(2-aminopyrimidin-4-yl)thiophene-2-carboxamide	659402: Displacement of fluorescent-ARC-1063 from His6-tagged recombinant human ROCK2 by luminescence intensity assay	kd	<0.0001	uM
N-[(2R)-6-amino-1-[[6-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxohexan-2-yl]-8-(4-isoquinolin-5-ylsulfonyl-1,4-diazepan-1-yl)octanamide	659402: Displacement of fluorescent-ARC-1063 from His6-tagged recombinant human ROCK2 by luminescence intensity assay	kd	<0.0001	uM
5-methyl-N-[6-(4-oxo-3H-phthalazin-1-yl)spiro[3.3]heptan-2-yl]-1-phenylpyrazole-4-carboxamide	2029384: Inhibition of ROCK2 (unknown origin)	ic50	0.0002	uM
N-[(1R)-1-(3-methoxyphenyl)ethyl]-6-methyl-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1675418: Inhibition of ROCK2 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH as substrate by caliper assay	ic50	0.0002	uM
(2S)-3-amino-2-[4-(hydroxymethyl)phenyl]-N-isoquinolin-6-ylpropanamide	1674171: Inhibition of human ROCK2 expressed in baculovirus expression system by Kinase-Glo luminescent Assay	ki	0.0002	uM
6-ethyl-N-[(1S)-1-(3-methoxyphenyl)ethyl]-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1925398: Inhibition of ROCK2 (unknown origin)	ic50	0.0002	uM
4-amino-1-[3-[[[3-(1H-indazol-5-ylamino)cyclohexyl]amino]methyl]phenyl]pyrimidin-2-one	2038258: Inhibition of ROCK2 (unknown origin) by HTRF assay	ic50	0.0002	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715183: Inhibition of human ROCK2 using KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK as substrate by [gamma-33P]-ATP assay	ic50	0.0002	uM
3-amino-2-[4-(hydroxymethyl)phenyl]-N-isoquinolin-6-ylpropanamide	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0002	uM
N-[(2R)-1-[[6-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-6-[[2-[24-(hydroxy-methylidene-oxo-lambda6-sulfanyl)-5,5,27,27-tetramethyl-16-oxa-12-aza-20-azoniaheptacyclo[15.11.0.03,15.04,12.06,11.020,28.021,26]octacosa-1,3,6(11),7,9,20(28),21(26),22,24-nonaen-8-yl]acetyl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-8-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]octanamide	659384: Binding affinity to His6-tagged recombinant human ROCK2 by fluorescence anisotropy assay	kd	0.0002	uM
3-[[(2R)-6-amino-1-[[N-[(4R)-5-amino-4-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[6-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]hexanoylamino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]-5-oxopentyl]carbamimidoyl]amino]-1-oxohexan-2-yl]carbamoyl]-4-[3,6-bis(dimethylamino)-3H-xanthen-9-yl]benzoic acid	659384: Binding affinity to His6-tagged recombinant human ROCK2 by fluorescence anisotropy assay	kd	0.0002	uM
6-ethyl-N-[(1R)-1-(3-methoxyphenyl)ethyl]-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1226640: Inhibition of ROCK2 (unknown origin) using substrate FITC-AHA- AKRRRLSSLRA-OH	ic50	0.0002	uM
N-[(1R)-1-(3-methoxyphenyl)ethyl]-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1675418: Inhibition of ROCK2 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH as substrate by caliper assay	ic50	0.0003	uM
methyl 3-[[(6-methyl-6H-isochromeno[3,4-c]pyridine-8-carbonyl)amino]methyl]benzoate	1925398: Inhibition of ROCK2 (unknown origin)	ic50	0.0003	uM
3-methoxy-N-[(1R)-1-(3-methoxyphenyl)ethyl]-4-(1H-pyrazol-4-yl)benzamide	1675403: Inhibition of ROCK2 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH peptide substrate by caliper assay	ic50	0.0003	uM
N-[(1S)-2-amino-1-phenylethyl]-3-methoxy-4-(1H-pyrazol-4-yl)benzamide	1675403: Inhibition of ROCK2 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH peptide substrate by caliper assay	ic50	0.0003	uM
(2S)-3-amino-N-isoquinolin-6-yl-2-phenylpropanamide	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0004	uM
3-ethyl-N-[(1R)-1-(3-methoxyphenyl)ethyl]-4-(1H-pyrazol-4-yl)benzamide	1675403: Inhibition of ROCK2 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH peptide substrate by caliper assay	ic50	0.0004	uM
N-[2-(dimethylamino)ethyl]-N-[(3-methoxyphenyl)methyl]-6-(1H-pyrazol-4-yl)-1,3-benzothiazole-2-carboxamide	467844: Inhibition of ROCK2	ic50	0.0004	uM
3-amino-N-isoquinolin-6-yl-2-(4-methylphenyl)propanamide	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0004	uM
1-[(3-hydroxyphenyl)methyl]-3-(4-pyridin-4-yl-1,3-thiazol-2-yl)urea;methanesulfonic acid	1119752: Inhibition of ROCK2 (unknown origin)	ic50	0.0004	uM
3-amino-2-(4-chlorophenyl)-N-isoquinolin-6-ylpropanamide	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0004	uM
N-[[3-[[(2S)-1-ethylpyrrolidin-2-yl]methylcarbamoyl]phenyl]methyl]-6-methyl-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1675418: Inhibition of ROCK2 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH as substrate by caliper assay	ic50	0.0005	uM
[2-methoxy-3-(4,5,10-triazatetracyclo[7.7.0.02,6.012,16]hexadeca-1(9),2(6),3,7,10,12(16)-hexaen-11-yl)phenyl]boronic acid	1564120: Inhibition of human ROCK2 using KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK as substrate incubated for 20 mins in presence of [gamma33P]ATP by filter binding method	ic50	0.0005	uM
N-[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]hexanamide	659375: Displacement of fluorescent-ARC-1042 from His6-tagged recombinant human ROCK2 by fluorescence anisotropy assay	kd	0.0005	uM
[2-methoxy-3-(3H-pyrazolo[4,5-f]quinolin-7-yl)phenyl]boronic acid	1925398: Inhibition of ROCK2 (unknown origin)	ic50	0.0005	uM
N-[(1R)-1-(3-methoxyphenyl)ethyl]-5H-chromeno[3,4-c]pyridine-8-carboxamide	1226640: Inhibition of ROCK2 (unknown origin) using substrate FITC-AHA- AKRRRLSSLRA-OH	ic50	0.0005	uM
N-(4-pyridin-4-yl-1,3-thiazol-2-yl)-2,3-dihydro-1,4-benzodioxine-3-carboxamide	1119754: Inhibition of N-terminal GST-tagged ROCK2 (1 to 552) (unknown origin) using KKRPQRRSNVF as substrate after 1 hr by Z-Lyte-based FRET assay	ic50	0.0006	uM
3-amino-2-(4-hydroxyphenyl)-N-isoquinolin-6-ylpropanamide	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0006	uM
3-chloro-N-[(1R)-1-(3-methoxyphenyl)ethyl]-4-(1H-pyrazol-4-yl)benzamide	1675403: Inhibition of ROCK2 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH peptide substrate by caliper assay	ic50	0.0007	uM
6-cyclopropyl-N-[(1R)-1-(3-methoxyphenyl)ethyl]-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1675418: Inhibition of ROCK2 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH as substrate by caliper assay	ic50	0.0007	uM
[4-[3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl pyridine-3-carboxylate	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0007	uM
3-amino-N-isoquinolin-6-yl-2-naphthalen-2-ylpropanamide	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0007	uM
4-amino-1-[4-[[[3-(1H-indazol-5-ylamino)cyclohexyl]amino]methyl]phenyl]pyrimidin-2-one	2038258: Inhibition of ROCK2 (unknown origin) by HTRF assay	ic50	0.0007	uM
[4-[(2S)-3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 3-(nitrooxymethyl)benzoate;methanesulfonic acid	2129255: Inhibition of ROCK2 (unknown origin) incubated for 60 mins in presence of ATP by mobility shift assay	ic50	0.0007	uM
N-[2-[2-(dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl]-6-methoxy-3,4-dihydro-2H-chromene-3-carboxamide	1639055: Inhibition of ROCK2 (unknown origin) using STK2 as substrate measured after 4 hrs by HTRF assay	ic50	0.0007	uM
(2R)-6-amino-N-[6-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]-2-[3-[[2-[[2-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]-2-oxoethyl]amino]acetyl]amino]propanoylamino]hexanamide	659375: Displacement of fluorescent-ARC-1042 from His6-tagged recombinant human ROCK2 by fluorescence anisotropy assay	kd	0.0007	uM
N-[[3-(ethylcarbamoyl)phenyl]methyl]-6-methyl-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1675418: Inhibition of ROCK2 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH as substrate by caliper assay	ic50	0.0008	uM
[4-[3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 2-phenylacetate	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0008	uM
3-amino-2-(2,4-dichlorophenyl)-N-isoquinolin-6-ylpropanamide	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0008	uM
N-[[3-(ethylcarbamoyl)phenyl]methyl]-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1675418: Inhibition of ROCK2 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH as substrate by caliper assay	ic50	0.0008	uM
N-[[3-[(1-methylazetidin-3-yl)carbamoyl]phenyl]methyl]-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1675418: Inhibition of ROCK2 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH as substrate by caliper assay	ic50	0.0008	uM
[4-[3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 4-(nitrooxymethyl)benzoate;methanesulfonic acid	2129255: Inhibition of ROCK2 (unknown origin) incubated for 60 mins in presence of ATP by mobility shift assay	ic50	0.0008	uM
3-amino-N-isoquinolin-6-yl-2-phenylpropanamide	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0008	uM
4-[4-[(2-aminopyrimidin-4-yl)amino]-2,6-difluorophenoxy]-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile	2194068: Inhibition of His-tagged human ROCK2 expressed in Sf9 cells pre-incubated for 10 mins before S6 peptide substrate addition in presence of [33P]ATP and measured after 20 mins by scintillation counting	ic50	0.0009	uM
3-amino-2-(3-chlorophenyl)-N-isoquinolin-6-ylpropanamide	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0009	uM
N-[3-(dimethylamino)propyl]-3-[6-(1H-pyrazol-4-yl)-1,3-benzothiazol-2-yl]-3,4-dihydro-2H-chromene-6-carboxamide	467844: Inhibition of ROCK2	ic50	0.0009	uM
[4-[3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 3,5-dimethylbenzoate	1295064: Inhibition of ROCK2 (unknown origin) using RSK2 peptide (KKRNRTLTK) as substrate after 180 mins by luminescent kinase assay	ki	0.0009	uM
6-chloro-4-N-[3,5-difluoro-4-[(3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]phenyl]pyrimidine-2,4-diamine	1953162: Inhibition of ROCK2 (unknown origin)	ic50	0.0010	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, decreases expression	5
Dexamethasone	decreases reaction, increases expression, affects cotreatment	3
Endosulfan	decreases expression	3
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	increases expression, increases methylation, affects cotreatment	2
trichostatin A	increases expression	2
cobaltous chloride	decreases expression, increases expression	2
ochratoxin A	increases expression	2
potassium chromate(VI)	decreases expression, affects cotreatment	2
chromium hexavalent ion	decreases expression, increases abundance, increases expression	2
Fulvestrant	decreases reaction, increases expression, increases methylation	2
Indomethacin	affects cotreatment, increases expression, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression, increases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
moringin	affects cotreatment, decreases expression	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	increases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
bis(tri-n-butyltin)oxide	increases expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	increases expression	1
tributyltin	increases expression	1
tetrahydropalmatine	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1

ChEMBL screening assays

788 unique, capped per target: 783 binding, 3 functional, 1 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3405453	Binding	Inhibition of ROCK (unknown origin)	Isosteric replacements of the carboxylic acid of drug candidate VX-787: Effect of charge on antiviral potency and kinase activity of azaindole-based influenza PB2 inhibitors. — Bioorg Med Chem Lett
CHEMBL915977	Functional	Inhibition of TPA-induced Rho kinase dependent MBS phosphorylation in MDCK 2 cells	Design and synthesis of rho kinase inhibitors (III). — Bioorg Med Chem
CHEMBL4424908	ADMET	Inhibition of human N-terminal His6-tagged (11 to 552 residues) ROCK2 expressed in baculovirus infected Sf21 insect cells using Long S6 Kinase as substrate	Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952. — Bioorg Med Chem Lett

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2E1	Abcam HeLa ROCK2 KO	Cancer cell line	Female
CVCL_B7Z6	Abcam Raji ROCK2 KO	Cancer cell line	Male
CVCL_B9ZX	Abcam THP-1 ROCK2 KO	Cancer cell line	Male
CVCL_C7BL	Abcam PC-3 ROCK2 KO	Cancer cell line	Male
CVCL_D7ZK	Ubigene A-549 ROCK2 KO	Cancer cell line	Male
CVCL_D8UQ	Ubigene HCT 116 ROCK2 KO	Cancer cell line	Male
CVCL_TJ50	HAP1 ROCK2 (-) 1	Cancer cell line	Male
CVCL_TJ51	HAP1 ROCK2 (-) 2	Cancer cell line	Male
CVCL_TJ52	HAP1 ROCK2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE