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): 163 total
• Regional missense constraint (gnomAD): 1 of 6 regions constrained (≈1% of expected missense variation)
• GTEx eGene: eQTL in 22 tissues, sQTL in 4 (q < 0.05)
• Drug target: yes — 1 curated mechanism-of-action drug, 9 via a complex or family; 52 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 1 — Belumosudil
• Approved drugs acting on a complex or family including it: 1 — Netarsudil Dimesylate (Rho-associated protein kinase)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.35 (highly constrained)
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_004850
• Interaction hub: 2,474 STRING partners (top 4% of genes corpus-wide)
• Notable: 163 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 25 — 17 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000315872

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 3, TSL 4: 1, TSL 5: 1

ENST00000315872, ENST00000261535, ENST00000401753, ENST00000431087, ENST00000460262, ENST00000462366, ENST00000484951, ENST00000493096, ENST00000697752, ENST00000697790, ENST00000697791, ENST00000697792, ENST00000944889, ENST00000944890, ENST00000944891, ENST00000983263, ENST00001056339, ENST00001056340, ENST00001056341, ENST00001056342, ENST00001110118, ENST00001114548, ENST00001114549, ENST00001125731, ENST00001145037

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.

Highest expression (Bgee): calcaneal tendon, colonic epithelium, middle temporal gyrus, diaphragm, biceps brachii.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ROCK2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 22 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 26 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellum	eqtl	9.3e-13	-0.32	2:11397326:T:C
Brain Cerebellar Hemisphere	eqtl	1.1e-12	-0.30	2:11397326:T:C
Muscle Skeletal	eqtl	3.4e-11	-0.17	2:11417674:G:A
Cells EBV-transformed lymphocytes	eqtl	3.0e-09	+0.46	2:11253015:C:CT
Whole Blood	eqtl	7.3e-09	-0.13	2:11349405:A:G
Artery Aorta	eqtl	2.2e-06	+0.21	2:11372186:C:T
Muscle Skeletal	sqtl	8.6e-06	-0.32	2:11183748:TA:T
Brain Hypothalamus	eqtl	9.9e-05	+0.24	2:11168025:G:A
Adipose Subcutaneous	eqtl	1.5e-04	-0.20	2:11252405:G:C
Cells Cultured fibroblasts	eqtl	3.0e-04	-0.23	2:11363329:C:T
Spleen	eqtl	3.8e-04	-0.16	2:11415980:G:A
Artery Tibial	eqtl	6.9e-04	-0.22	2:11166693:C:T
Uterus	eqtl	1.0e-02	+0.37	2:10784567:G:A
Pituitary	eqtl	1.1e-02	-1.19	2:11395758:G:T
Adipose Subcutaneous	sqtl	1.1e-02	+0.65	2:10773098:C:T
Artery Coronary	eqtl	1.4e-02	+0.61	2:10354485:G:A
Skin Sun Exposed Lower leg	eqtl	1.7e-02	-0.08	2:11436287:C:A
Heart Left Ventricle	sqtl	1.9e-02	-0.46	2:11396491:G:T
Colon Sigmoid	sqtl	2.2e-02	-1.62	2:10746161:G:A
Esophagus Muscularis	eqtl	2.3e-02	+0.28	2:11515498:T:C

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

showing 100 of 300 tissues 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
gastrocnemius	UBERON:0001388	91.38	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.31	gold quality
muscle organ	UBERON:0001630	91.27	gold quality
skeletal muscle organ	UBERON:0014892	91.27	gold quality
muscle tissue	UBERON:0002385	91.20	gold quality
postcentral gyrus	UBERON:0002581	91.13	gold quality
muscle of leg	UBERON:0001383	91.07	gold quality
superior frontal gyrus	UBERON:0002661	90.83	gold quality
adipose tissue	UBERON:0001013	90.78	gold quality
aorta	UBERON:0000947	90.74	gold quality
visceral pleura	UBERON:0002401	90.67	gold quality
adrenal tissue	UBERON:0018303	90.67	gold quality
seminal vesicle	UBERON:0000998	90.63	gold quality
connective tissue	UBERON:0002384	90.63	gold quality
parietal lobe	UBERON:0001872	90.35	gold quality
saphenous vein	UBERON:0007318	90.32	gold quality
tibialis anterior	UBERON:0001385	90.28	gold quality
jejunal mucosa	UBERON:0000399	90.05	gold quality
decidua	UBERON:0002450	90.04	gold quality
orbitofrontal cortex	UBERON:0004167	90.01	gold quality
gluteal muscle	UBERON:0002000	89.90	gold quality
descending thoracic aorta	UBERON:0002345	89.86	gold quality
jejunum	UBERON:0002115	89.81	gold quality
ventricular zone	UBERON:0003053	89.72	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.66	gold quality
mucosa of urinary bladder	UBERON:0001259	89.64	gold quality
primary visual cortex	UBERON:0002436	89.63	gold quality
middle frontal gyrus	UBERON:0002702	89.62	gold quality
omental fat pad	UBERON:0010414	89.50	gold quality
peritoneum	UBERON:0002358	89.49	gold quality
right coronary artery	UBERON:0001625	89.46	gold quality
skin of hip	UBERON:0001554	89.28	gold quality
left coronary artery	UBERON:0001626	89.24	gold quality
pleura	UBERON:0000977	89.12	gold quality
thoracic aorta	UBERON:0001515	89.09	gold quality
occipital lobe	UBERON:0002021	89.08	gold quality
ascending aorta	UBERON:0001496	88.98	gold quality
coronary artery	UBERON:0001621	88.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.92	gold quality
lung	UBERON:0002048	88.91	gold quality
tibia	UBERON:0000979	88.89	gold quality
myometrium	UBERON:0001296	88.89	gold quality
body of uterus	UBERON:0009853	88.76	gold quality
tendon	UBERON:0000043	88.66	gold quality
parietal pleura	UBERON:0002400	88.61	gold quality
paraflocculus	UBERON:0005351	88.60	gold quality
urethra	UBERON:0000057	88.39	gold quality
pericardium	UBERON:0002407	88.24	gold quality
ileal mucosa	UBERON:0000331	87.99	gold quality
placenta	UBERON:0001987	87.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.83	gold quality
lower esophagus	UBERON:0013473	87.82	gold quality
heart right ventricle	UBERON:0002080	87.81	gold quality
islet of Langerhans	UBERON:0000006	87.78	gold quality
sural nerve	UBERON:0015488	87.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.69	gold quality
right lung	UBERON:0002167	87.58	gold quality
duodenum	UBERON:0002114	87.56	gold quality
upper lobe of left lung	UBERON:0008952	87.34	gold quality
upper lobe of lung	UBERON:0008948	87.31	gold quality
lower lobe of lung	UBERON:0008949	87.27	gold quality
gall bladder	UBERON:0002110	87.21	gold quality
cortical plate	UBERON:0005343	87.08	gold quality
thoracic mammary gland	UBERON:0005200	87.02	gold quality
uterus	UBERON:0000995	87.00	gold quality
trabecular bone tissue	UBERON:0002483	86.90	gold quality
cerebellum	UBERON:0002037	86.88	gold quality
mammary gland	UBERON:0001911	86.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.75	gold quality
frontal cortex	UBERON:0001870	86.60	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebellum	tissue	63.5	medium
Cerebral cortex	tissue	53.9	medium
Occipital cortex	tissue	53.9
Somatosensory cortex	tissue	51.5
Hippocampal formation	tissue	48.5
Prefrontal cortex	tissue	48.3
Postcentral gyrus	tissue	48.3
Retrosplenial and cingulate cortex	tissue	48.2
Motor cortex	tissue	48.1
Entorhinal cortex	tissue	48.1
Retrosplenial cortex	tissue	47.3
Frontal cortex	tissue	47.1
Temporal cortex	tissue	45.1
Nucleus accumbens	tissue	44.4
Caudate putamen	tissue	44.3
Insular cortex	tissue	42.9
Putamen	tissue	42.5
Hippocampus	tissue	40.3	medium
Basal ganglia	tissue	37.0	low
Amygdala	tissue	35.2
Ventral forebrain	tissue	33.9
Adipose tissue	tissue	33.5	not detected
Olfactory bulb	tissue	33.1
Thalamus	tissue	30.9
Superior colliculi	tissue	30.6
Corpus callosum	tissue	30.4
Midbrain	tissue	29.4
Skeletal muscle	tissue	29.3	low
Septum	tissue	29.0
Tongue	tissue	28.3
Locus coeruleus	tissue	26.6
Pons	tissue	26.2
Spinal cord	tissue	25.8
Smooth muscle	tissue	25.5	low
Medulla oblongata	tissue	24.8
Rectum	tissue	24.0	medium
Substantia nigra	tissue	23.4
Hypothalamus	tissue	23.0
Placenta	tissue	22.7	medium
Periaqueductal gray	tissue	22.7
Choroid plexus	tissue	22.4
Colon	tissue	20.8	low
Endometrium 1	tissue	20.2	medium
Urinary bladder	tissue	17.8	medium
Small intestine	tissue	17.6	medium
Cervix	tissue	17.3	medium
Seminal vesicle	tissue	17.1	low
Heart muscle	tissue	16.4	not detected
Prostate	tissue	16.2	medium
Liver	tissue	15.4	not detected
Lung	tissue	15.2	medium
Spleen	tissue	15.1	medium
Duodenum	tissue	15.1	medium
Ovary	tissue	14.8	low
Esophagus	tissue	14.8	medium
Gallbladder	tissue	14.1	medium
Breast	tissue	13.8	medium
Salivary gland	tissue	13.8	medium
Kidney	tissue	13.4	not detected
Stomach 1	tissue	13.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Cerebellar cortex (58.4), Vermis (58.0), Flocculonodular lobe (55.1), Caudate nucleus (51.8), Transversal temporal gyrus, anterior (50.0).

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)

Targeting ROCK2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 290 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.346, missense Z 4.3 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000315872 splits into 6 regions with different missense tolerance; 1 is missense-constrained (≈1% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:11,183,440–11,197,342	221 / 355.1	0.62	no
2:11,197,343–11,197,564	0 / 17.5	0.00	yes (p 2.9e-05)
2:11,197,565–11,198,537	29 / 75.0	0.39	no
2:11,198,538–11,221,211	542 / 672.0	0.81	no
2:11,221,212–11,344,015	253 / 455.5	0.56	no
2:11,344,016–11,344,136	64 / 62.4	1.03	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:107926) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 31 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body size	2
abnormal circulating cholesterol level	1
abnormal heart morphology	1
decreased body weight	1
retina degeneration	1
reduced long-term potentiation	1
abnormal cardiovascular system physiology	1
abnormal placenta morphology	1
hemorrhage	1
premature death	1
abnormal extraembryonic tissue morphology	1
abnormal cardiovascular system morphology	1
decreased circulating free fatty acids level	1
abnormal excitatory postsynaptic potential	1
decreased paired-pulse facilitation	1
abnormal cytokine secretion	1
ocular hypotension	1
improved glucose tolerance	1
abnormal heart size	1
abnormal vascular smooth muscle physiology	1
decreased susceptibility to diet-induced obesity	1
retina neovascularization	1
abnormal synapse morphology	1
lethality, incomplete penetrance	1
embryonic lethality, complete penetrance	1

+6 more (showing top 25).

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Pan troglodytes	P61584	100.0%	Diamond
Mycobacterium tuberculosis variant bovis AF2122/97	P65731	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WI68	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WI69	100.0%	Diamond
Pongo abelii	Q5R8M1	100.0%	Diamond
Bos taurus	A2VDV2	99.4%	Diamond
Drosophila pseudoobscura pseudoobscura	Q2LZZ7	97.6%	Diamond
Caenorhabditis briggsae	A8XJL7	96.4%	Diamond
Oryctolagus cuniculus	O77819	95.7%	Diamond
Sus scrofa	M3TYT0	94.8%	Diamond
Ailuropoda melanoleuca	D2HXI8	88.7%	Diamond
Canis lupus familiaris	E2RJI4	88.7%	Diamond
Xenopus tropicalis	B1WAR9	87.3%	Diamond
Xenopus laevis	Q6NTJ3	87.3%	Diamond
Gallus gallus	Q5F361	87.0%	Diamond
Eremothecium gossypii ATCC 10895	Q754N7	86.2%	Diamond
Nakaseomyces glabratus CBS 138	Q6FP74	84.2%	Diamond
Mycobacterium leprae TN	P57993	83.2%	Diamond
Candida albicans SC5314	Q5AP53	79.5%	Diamond
Debaryomyces hansenii CBS767	Q6BLJ9	79.5%	Diamond
Saccharomyces cerevisiae S288C	P53894	79.0%	Diamond
Kluyveromyces lactis NRRL Y-1140	P31034	76.9%	Diamond
Streptomyces griseus	P54742	71.4%	Diamond
Schizosaccharomyces pombe 972h-	O13310	67.9%	Diamond
Pneumocystis carinii	Q6TGC6	67.9%	Diamond
Yarrowia lipolytica CLIB122	Q6CFS5	67.7%	Diamond
Neurospora crassa OR74A	P38679	59.4%	Diamond
Dictyostelium discoideum	Q54Y26	50.6%	Diamond
Arabidopsis thaliana	Q84VX4	46.7%	Diamond
Toxoplasma gondii	Q2PAY2	41.8%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
CIMIP5	protein-coding	130813
SLC66A3	protein-coding	130814
LINC00570	ncRNA	100874055
PPIAP60	protein-coding	107985791
FLJ33534	ncRNA	285150
KCNF1	protein-coding	3754

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, D6REE7, E9PF63, O75116

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. Interacts with FOXM1 isoform 5 (FOXM1D); the interaction promotes ROCK2 activation.

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

Enzyme classification (BRENDA)

• EC 2.7.11.39 — ROCK-subfamily protein kinase (BRENDA: 3 organisms, 31 substrates, 65 inhibitors, 6 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
KADRKKRYTVVGNPYWM	0.0032	1
KPARKKRYTVVGNPYWM	0.0036	1
KSARKKRYTVVGNPYWM	0.0017	1
KSDRKKRYTVVGNPYWM	0.0033	1
RAKYKTLRQIR	0.0019	1
[S6 PEPTIDE]-L-SERINE	0.0009	1

Catalyzed reactions (Rhea)

• 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 (75 total): helix 26, strand 12, region of interest 6, modified residue 6, domain 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)

23 structures by resolution:

PDB	Title	Method	Resolution (Å)
8X92	Crystal structure of ROCK2 with GNS-2666 inhibitor	X-RAY DIFFRACTION	2.2
7JNT	CRYSTAL STRUCTURE OF RHO-ASSOCIATED PROTEIN KINASE 2 (ROCK2) IN COMPLEX WITH A POTENT AND …	X-RAY DIFFRACTION	2.21
7JOV	CRYSTAL STRUCTURE OF RHO-ASSOCIATED PROTEIN KINASE 2 (ROCK2) IN COMPLEX WITH A …	X-RAY DIFFRACTION	2.59
8X8X	Crystal structure of ROCK2 with GNS-2591 inhibitor	X-RAY DIFFRACTION	2.6
9EP8	Crystal structure of ROCK2 in complex with a 8-(azaindolyl)-benzoazepinone inhibitor	X-RAY DIFFRACTION	2.63
6P5M	Discovery of a Novel, Highly Potent, and Selective Thieno[3,2-d]pyrimidinone-Based Cdc7 …	X-RAY DIFFRACTION	2.65
8X8Z	Crystal structure of ROCK2 with GNS-2664 inhibitor	X-RAY DIFFRACTION	2.7
8GDS	CRYSTAL STRUCTURE OF RHO-ASSOCIATED PROTEIN KINASE 2 (ROCK2) IN COMPLEX WITH …	X-RAY DIFFRACTION	2.71
7P6O	ROCK2 IN COMPLEX WITH COMPOUND 8	X-RAY DIFFRACTION	2.75
4L6Q	ROCK2 in complex with benzoxaborole	X-RAY DIFFRACTION	2.79
7P6P	ROCK2 IN COMPLEX WITH COMPOUND 17	X-RAY DIFFRACTION	2.82
6ED6	Crystal structure of Rock2 with a pyridinylbenzamide based inhibitor	X-RAY DIFFRACTION	2.86
7P6Q	ROCK2 IN COMPLEX WITH COMPOUND 21	X-RAY DIFFRACTION	2.89
9HFP	ROCK2 IN COMPLEX WITH CPD7	X-RAY DIFFRACTION	2.92
4WOT	ROCK2 IN COMPLEX WITH 1426382-07-1	X-RAY DIFFRACTION	2.93
9Q9T	Human ROCK2 in complex with a dihydropyrazolo-pyrimidine inhibitor	X-RAY DIFFRACTION	2.96
7P6N	ROCK2 IN COMPLEX WITH COMPOUND 12	X-RAY DIFFRACTION	3
9JCU	Compound bound to ROCK2 kinase domain	X-RAY DIFFRACTION	3.02
5U7Q	Identification of A New Class of Potent Cdc7 Inhibitors Designed by Putative …	X-RAY DIFFRACTION	3.15
8X8Y	Crystal structure of ROCK2 with GNS-2660 inhibitor	X-RAY DIFFRACTION	3.2
6P5P	Discovery of a Novel, Highly Potent, and Selective Thieno[3,2-d]pyrimidinone-Based Cdc7 …	X-RAY DIFFRACTION	3.3
5U7R	Identification of A New Class of Potent Cdc7 Inhibitors Designed by Putative …	X-RAY DIFFRACTION	3.33
9HJQ	ROCK2 bound with TDI01	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

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

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

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

Catalytic / active sites (2)

Position	Role
214	proton acceptor
1131–1132	cleavage; by granzyme b

Ligand- & substrate-binding residues (2)

Position	Role
98–106	ATP
121	ATP

Post-translational modifications (6)

Type	Positions
Phosphothreonine	414, 1212
Phosphotyrosine	722
Phosphoserine	1137, 1362, 1374

Mutagenesis-validated functional residues (1)

Position	Phenotype
1131	abolishes cleavage by granzyme b.

Function

Pathways and Gene Ontology

Reactome pathways

8 curated (TAS) of 32; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

32 pathways:

ID	Pathway	Evidence
R-HSA-9679191	Potential therapeutics for SARS ⚕	curated
R-HSA-416482	G alpha (12/13) signalling events	curated
R-HSA-8980692	RHOA GTPase cycle	curated
R-HSA-9013026	RHOB GTPase cycle	curated
R-HSA-9013422	RHOBTB1 GTPase cycle	curated
R-HSA-9013106	RHOC GTPase cycle	curated
R-HSA-9013407	RHOH GTPase cycle	curated
R-HSA-4420097	VEGFA-VEGFR2 Pathway	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-422475	Axon guidance	—
R-HSA-1266738	Developmental Biology	—
R-HSA-2682334	EPH-Ephrin signaling	—
R-HSA-3928663	EPHA-mediated growth cone collapse	electronic
R-HSA-3928662	EPHB-mediated forward signaling	electronic
R-HSA-388396	GPCR downstream signalling	—
R-HSA-9675108	Nervous system development	—
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-5627117	RHO GTPases Activate ROCKs	electronic
R-HSA-9706574	RHOBTB GTPase Cycle	—
R-HSA-400685	Sema4D in semaphorin signaling	—
R-HSA-416572	Sema4D induced cell migration and growth-cone collapse	electronic
R-HSA-373755	Semaphorin interactions	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—
R-HSA-194138	Signaling by VEGF	—

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 (53): 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), regulation of cell junction assembly (GO:1901888), positive regulation of amyloid-beta formation (GO:1902004), positive regulation of protein localization to early endosome (GO:1902966), positive regulation of amyloid precursor protein catabolic process (GO:1902993), regulation of establishment of endothelial barrier (GO:1903140), negative regulation of bicellular tight junction assembly (GO:1903347), cellular response to acetylcholine (GO:1905145), positive regulation of connective tissue replacement (GO:1905205), response to angiotensin (GO:1990776), regulation of establishment of cell polarity (GO:2000114), regulation of cell motility (GO:2000145), signal transduction (GO:0007165), regulation of amyloid-beta formation (GO:1902003)

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 (8): 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)

Reactome top-level categories

13 top-level categories:

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

showing 60 of 75 GO namespaces:

Category	Terms
actin cytoskeleton organization	3
cellular anatomical structure	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
connective tissue growth factor production	1
regulation of connective tissue growth factor production	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
enzyme binding	1
nucleic acid binding	1
molecular_function	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
transition metal ion binding	1
GTPase binding	1
cytoskeletal protein binding	1
endopeptidase activity	1
peptidase activator activity	1
endopeptidase regulator activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 25 of 79 annotations. The rest are phylogenetic / computational / electronic (IEA).

25 experimentally-supported GO terms:

GO term	NS	Evidence
Rho protein signal transduction	BP	direct assay
centrosome duplication	BP	mutant phenotype
host-mediated perturbation of viral process	BP	mutant phenotype
negative regulation of angiogenesis	BP	mutant phenotype
negative regulation of bicellular tight junction assembly	BP	genetic interaction
negative regulation of nitric oxide biosynthetic process	BP	mutant phenotype
negative regulation of protein localization to lysosome	BP	mutant phenotype
positive regulation of amyloid precursor protein catabolic process	BP	mutant phenotype
positive regulation of amyloid-beta formation	BP	mutant phenotype
positive regulation of cell migration	BP	mutant phenotype
positive regulation of protein localization to early endosome	BP	mutant phenotype
positive regulation of stress fiber assembly	BP	direct assay
protein localization to plasma membrane	BP	mutant phenotype
protein phosphorylation	BP	direct assay
regulation of establishment of endothelial barrier	BP	mutant phenotype
regulation of keratinocyte differentiation	BP	mutant phenotype
centrosome	CC	direct assay
cytoplasm	CC	direct assay
cytoplasmic ribonucleoprotein granule	CC	direct assay
cytosol	CC	direct assay
RNA binding	MF	high-throughput assay
Rho-dependent protein serine/threonine kinase activity	MF	mutant phenotype
endopeptidase activator activity	MF	mutant phenotype
protease binding	MF	physical interaction
protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,474 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ROCK2	RHOA	P06749	883
ROCK2	MYL2	P10916	771
ROCK2	MYH14	Q7Z406	740
ROCK2	CFL2	Q9Y281	739
ROCK2	CFL1	P23528	735
ROCK2	PDCD10	Q9BUL8	698
ROCK2	KRIT1	O00522	690
ROCK2	PPP1R12A	O14974	673
ROCK2	RND3	P52199	637
ROCK2	CCM2	Q9BSQ5	610
ROCK2	ITGB1BP1	O14713	608
ROCK2	RHOC	P08134	586
ROCK2	CDC42	P21181	576
ROCK2	ARHGEF1	Q92888	533
ROCK2	ITGB1	P05556	529

IntAct

Human interaction partners of ROCK2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 36 partners by confidence:

Partner	Interaction type	MIscore	Records
RPS6KA3	association	0.640	3
APP	physical association	0.560	6
STAT3	physical association	0.520	3
PPP1R14B	phosphorylation reaction	0.440	1
JAK2	physical association	0.400	2
BATF	physical association	0.400	1
BCL6	physical association	0.400	1
BCL9L	physical association	0.400	1
CXCR5	physical association	0.400	1
EP300	physical association	0.400	1
H2BC21	physical association	0.400	1
HNRNPCL2	physical association	0.400	1
ICOS	physical association	0.400	1
IRF4	physical association	0.400	1
JAK3	physical association	0.400	1
MAF	physical association	0.400	1
NCL	physical association	0.400	1
PDCD1	physical association	0.400	1
RTP5	physical association	0.400	1
TOB1	physical association	0.400	1
TXLNA	physical association	0.400	1
ADD2	association	0.350	2
POLR1C	association	0.350	2
CLTB	association	0.350	1
DNAJC8	association	0.350	1
EGFL7	association	0.350	1
FLOT2	colocalization	0.350	1
HTRA3	association	0.350	1
SFXN2	association	0.350	1
SPRTN	association	0.350	1

BioGRID (203 interactions; top human partners by supporting records): RHOA (Affinity Capture-Western; 5 records), ROCK1 (Affinity Capture-MS; 5 records), DNAJB11 (Affinity Capture-MS; 4 records), BRCA2 (Affinity Capture-MS; 3 records), CDKN3 (Affinity Capture-Western; 3 records), KRAS (Proximity Label-MS; 3 records), POLR1C (Affinity Capture-MS; 3 records), RPS6KA3 (Affinity Capture-MS; 3 records), ADD2 (Affinity Capture-MS; 2 records), EGFR (Positive Genetic; 2 records), FBXO42 (Affinity Capture-MS; 2 records), HSPA8 (Co-fractionation; 2 records), KIAA1429 (Affinity Capture-RNA; 2 records), LAMP1 (Proximity Label-MS; 2 records), LMNA (Co-fractionation; 2 records)

SIGNOR signaling

showing 15 of 24 signaling 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

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ BRCA2-NPM1-ROCK2 complex	3	BRCA2, NPM1, ROCK2
★ EP300-ROCK2 complex	2	EP300, ROCK2
★ CORO1B-ROCK2 complex	2	CORO1B, ROCK2
★ Rho-associated protein kinase 2	1	ROCK2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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
Interleukin-4 and Interleukin-13 signaling	6	22.1×	3e-05
Signaling by Interleukins	8	18.3×	3e-06
Cytokine Signaling in Immune system	8	11.7×	3e-05

Disease & clinical

Genetic variants

Variant evidence for ROCK2: 163 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	104
Likely benign	9
Benign	6

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 41 predictions of 3,180):

Position(s)	Effect	Δscore	Sites
2:11183441–11183442	acceptor_loss	1.0000	5
2:11192449–11192450	donor_loss	1.0000	4
2:11192713–11192714	acceptor_loss	1.0000	4
2:11192715	acceptor_gain	1.0000
2:11194254–11194255	donor_loss	1.0000	5
2:11194345–11194346	acceptor_loss	1.0000	4
2:11194953–11194954	donor_loss	1.0000	5
2:11195026–11195027	acceptor_loss	1.0000	3
2:11197178–11197179	donor_loss	1.0000	4
2:11197349–11197350	acceptor_loss	1.0000	6

AlphaMissense

4,066 missense substitutions predicted likely pathogenic (of 9,274 scored), across 1,005 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M169	9	0.989	0.999
M128	9	0.982	0.999
M1107	9	0.961	0.998
M307	9	0.955	0.996
M144	9	0.922	0.999
M172	9	0.917	0.992
M220	9	0.888	0.999
M120	9	0.862	0.992
M945	9	0.853	0.984
D214	8	1.000	1.000
D232	8	1.000	1.000
N219	8	0.999	1.000
D255	8	0.999	1.000
D276	8	0.999	1.000
H1261	8	0.999	1.000
D176	8	0.998	1.000
H212	8	0.998	1.000
H1301	8	0.998	1.000
H206	8	0.997	0.999
F233	8	0.997	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.61e-05

Disease associations

OMIM: gene MIM:604002 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital heart disease	Moderate	Autosomal dominant	2

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Mondo (1): congenital heart disease (MONDO:0005453)

GWAS associations

4 associations:

Study	Trait	p-value
GCST90002397_299	Mean spheric corpuscular volume	6e-18
GCST90002388_122	Lymphocyte count	9e-13
GCST90000025_443	Appendicular lean mass	1e-11
GCST010245_44	LDL cholesterol levels	4e-8

EFO canonical traits (from GWAS)

3 canonical traits:

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

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ROCK2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
BELUMOSUDIL	Small molecule	4

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes ROCK2 — the drug acts on the assembly or class, not necessarily on this subunit alone.

9 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
NETARSUDIL DIMESYLATE	Rho-associated protein kinase	2	4
AMA0076	Rho-associated protein kinase	2	3
FASUDIL	Rho-associated protein kinase	2	3
RIPASUDIL	Rho-associated protein kinase	2	3
DE-104	Rho-associated protein kinase	2	2
SAR-407899	Rho-associated protein kinase	2	2
VEROSUDIL	Rho-associated protein kinase	2	2
AT-13148	Rho-associated protein kinase	2	1
Y-39983	Rho-associated protein kinase	2	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 264,448 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

52 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL2005186	BELUMOSUDIL	4	1,912
CHEMBL2105759	BARICITINIB	4	7,117
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL2325741	CAPIVASERTIB	4	2,281
CHEMBL2403108	CERITINIB	4	9,002
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL1078178	MOMELOTINIB	4	3,649
CHEMBL4594250	NETARSUDIL	4	1,095
CHEMBL189963	PALBOCICLIB	4	13,796
CHEMBL1789941	RUXOLITINIB	4	12,161
CHEMBL535	SUNITINIB	4	80,232
CHEMBL221959	TOFACITINIB	4	10,947
CHEMBL2103743	TOFACITINIB CITRATE	4	1,763
CHEMBL3622821	UPADACITINIB	4	2,949
CHEMBL24828	VANDETANIB	4	43,290
CHEMBL2219422	AFURESERTIB	3	1,534
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL522892	DOVITINIB	3	5,162
CHEMBL38380	FASUDIL	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL3426621	RIPASUDIL	3
CHEMBL1967878	CENISERTIB	2
CHEMBL3039513	DECERNOTINIB	2
CHEMBL541388	FASUDIL HYDROCHLORIDE	2
CHEMBL1230609	FORETINIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL1980715	LAUROGUADINE	2
CHEMBL1088751	PH-797804	2
CHEMBL475251	R-406	2
CHEMBL384304	RG-547	2
CHEMBL4594454	RIPASUDIL HYDROCHLORIDE DIHYDRATE	2
CHEMBL1667969	SAR-407899 FREE BASE	2
CHEMBL1721885	SU-014813	2
CHEMBL574737	UCN-01	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL3545065	VEROSUDIL	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL551064	AEW-541	1
CHEMBL574738	AST-487	1
CHEMBL3544960	AT-13148	1
CHEMBL482967	CYC-116	1
CHEMBL1090479	GSK-1070916	1
CHEMBL494089	GSK-690693	1
CHEMBL1908397	KW-2449	1
CHEMBL3356433	LX-7101	1
CHEMBL1084546	PF-00562271	1
CHEMBL482767	SNS-314	1
CHEMBL3545328	XL-019	1
CHEMBL571948	Y-39983	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Rho kinase

Most potent curated ligand interactions (22 total), top 22:

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
zilemaltib	Inhibition	7.99	pIC50
fimosudil	Inhibition	7.99	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)

4754 measured of 6067 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5407182	IC50	0.02 nM
CHEMBL5406146	IC50	0.023 nM
CHEMBL5414576	IC50	0.035 nM
CHEMBL5437264	IC50	0.053 nM
CHEMBL5428430	IC50	0.054 nM
CHEMBL5400934	IC50	0.083 nM
CHEMBL5408482	IC50	0.091 nM
US11427563, Compound 70	IC50	0.1 nM	US-11427563: Aryl cyclopropyl-amino-isoquinolinyl amide compounds
CHEMBL5438374	IC50	0.12 nM
CHEMBL6169753	KI	0.15 nM
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
CHEMBL5287722	IC50	0.18 nM
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
CHEMBL3792888	KI	0.2 nM
CHEMBL5397091	IC50	0.2 nM
CHEMBL5414146	IC50	0.2 nM
(1R)-N-(4-chloroisoquinolin-6-yl)-2-[4-(pyridin-2-ylsulfamoyl)phenyl]cyclopropane-1-carboxamide	IC50	0.2 nM	US-11427563: Aryl cyclopropyl-amino-isoquinolinyl amide compounds
US11427563, Compound 49	IC50	0.2 nM	US-11427563: Aryl cyclopropyl-amino-isoquinolinyl amide compounds
US11427563, Compound 53	IC50	0.2 nM	US-11427563: Aryl cyclopropyl-amino-isoquinolinyl amide compounds
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
CHEMBL5411877	IC50	0.22 nM
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-cyclopentyl-3-[(1R)-1-[2-(dimethylamino)ethyl-(4-pyridin-4-ylbenzoyl)amino]ethyl]benzamide	IC50	0.23 nM	US-10738007: Amide compounds as kinase inhibitors, compositions and methods of treatment
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
CHEMBL6175959	KI	0.28 nM
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
3-[(1S)-2-hydroxy-1-[(4-pyridin-4-ylbenzoyl)amino]ethyl]-N-[(1-methylpiperidin-4-yl)methyl]benzamide	IC50	0.3 nM	US-10738007: Amide compounds as kinase inhibitors, compositions and methods of treatment
N-[[4-[(dimethylamino)methyl]phenyl]methyl]-3-[(1R)-1-[(4-pyridin-4-ylbenzoyl)amino]ethyl]benzamide	IC50	0.3 nM	US-10738007: Amide compounds as kinase inhibitors, compositions and methods of treatment
N-[(1-methylpiperidin-4-yl)methyl]-3-[(1R)-1-[(4-pyridin-4-ylbenzoyl)amino]ethyl]benzamide	IC50	0.3 nM	US-10738007: Amide compounds as kinase inhibitors, compositions and methods of treatment
3-[(1S)-2-hydroxy-1-[(4-pyridin-4-ylbenzoyl)amino]ethyl]-N-[(1-propan-2-ylpiperidin-4-yl)methyl]benzamide	IC50	0.31 nM	US-10738007: Amide compounds as kinase inhibitors, compositions and methods of treatment
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

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

2059 with measured affinity, of 4892 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
N-[3-[4-oxo-7-(1H-pyrrolo[2,3-b]pyridin-4-yl)-2,5-dihydro-1H-3-benzazepin-3-yl]phenyl]methanesulfonamide	2259351: Inhibition of N-terminal-His6-tagged_ZB_TEV fused ROCK2 catalytic domain (19 to 417 residues) (unknown origin) expressed in insect High Five cells assessed as inhibition constant in presence of ATP at » Km concentration	ki	0.0001	uM
3-[3-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]-7-(1H-pyrrolo[2,3-b]pyridin-4-yl)-2,5-dihydro-1H-3-benzazepin-4-one	2259343: Inhibition of N-terminal-His6-tagged_ZB_TEV fused ROCK2 catalytic domain (19 to 417 residues) (unknown origin) expressed in insect High Five cells assessed as inhibition constant in presence of ATP at Km concentration	ki	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
3-phenyl-7-(1H-pyrrolo[2,3-b]pyridin-4-yl)-2,5-dihydro-1H-3-benzazepin-4-one	2259351: Inhibition of N-terminal-His6-tagged_ZB_TEV fused ROCK2 catalytic domain (19 to 417 residues) (unknown origin) expressed in insect High Five cells assessed as inhibition constant in presence of ATP at » Km concentration	ki	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, decreases expression, affects methylation	5
Dexamethasone	decreases reaction, increases expression, affects cotreatment	3
Endosulfan	decreases expression	3
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	increases methylation, affects cotreatment, increases expression	2
trichostatin A	increases expression	2
cobaltous chloride	decreases expression, increases expression	2
ochratoxin A	increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
chromium hexavalent ion	increases abundance, increases expression, decreases expression	2
Fulvestrant	decreases reaction, increases expression, increases methylation	2
Indomethacin	decreases expression, affects cotreatment, increases 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

10 cell lines: 9 cancer cell line, 1 transformed 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_F4V7	HyCyte HEK293T stable cell line for hROCK2 overexpression	Transformed cell line	Female
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)

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

showing 60 of 303 trials:

NCT	Phase	Status	Title
NCT00668824	Phase 4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	Phase 4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	Phase 4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	Phase 4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	Phase 4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	Phase 4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	Phase 4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	Phase 4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	Phase 4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	Phase 4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	Phase 4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	Phase 4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	Phase 3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	Phase 3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	Phase 3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	Phase 3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	Phase 3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	Phase 3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	Phase 3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	Phase 3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	Phase 3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	Phase 3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	Phase 3	UNKNOWN	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	Phase 3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	Phase 3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	Phase 3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	Phase 3	RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	Phase 2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	Phase 2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	Phase 2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	Phase 2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	Phase 2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	Phase 2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	Phase 2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	Phase 2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	Phase 2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	Phase 2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	Phase 2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	Phase 2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	Phase 2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE
NCT01841177	Phase 2	COMPLETED	Evaluating Precision of Therapy - Milrinone
NCT02046135	Phase 2	TERMINATED	Sodium Bicarbonate to Prevent Acute Kidney Injury in Children Undergoing Cardiac Surgery
NCT02133573	Phase 2	COMPLETED	Randomized Trial of Maternal Progesterone Therapy
NCT02232399	Phase 2	COMPLETED	Is Levosimendan Superior to Milrinone Regarding Acute Kidney Injury After Cardiac Surgery for Congenital Heart Disease?
NCT02492269	Phase 2	COMPLETED	Stress Response and Neurodevelopmental Outcome After Cardiac Surgery Utilizing CPB in Children: A Prospective, Double Blinded and Randomized Study
NCT02564796	Phase 2	TERMINATED	Erythropoietin to Prevent Unnecessary Transfusions In Patients With Cyanotic CHD - A Prospective Control Trial
NCT02618824	Phase 2	UNKNOWN	Role of Terminal Warm Blood Cardioplegia as Myocardial Protection in the Use of Histidine-Tryptophan-Ketoglutarate Cardioplegia in Complex Congenital Heart Surgery
NCT02769624	Phase 2	TERMINATED	Acute Effects of Inhaled Treprostinil in Fontan Patients
NCT02877238	Phase 2	COMPLETED	Remote Preconditioning and Myocardial Protection
NCT03082716	Phase 2	COMPLETED	Custodiol Versus Blood Cardioplegaia in Paediatric Cardiac Surgery
NCT03425734	Phase 2	UNKNOWN	The Effect of Dexmedetomidine on Kidney Perfusion in Paediatric Patients
NCT04434001	Phase 2	TERMINATED	ZEPLAST- PED: ZEro_PLASma Trial in Small Infants Undergoing Cardiac Surgery
NCT04807621	Phase 2	UNKNOWN	Platelets or Fibrinogen as First-line Treatment for Bleeding During Pedatric Heart Surgery
NCT05717049	Phase 2	COMPLETED	Theophylline Effects in the Fontan Circulation
NCT06080074	Phase 2	RECRUITING	Multicenter Trial of ECMO in Children With Severe Cardiac Failure Using the Cardiohelp System
NCT07498803	Phase 2	NOT_YET_RECRUITING	Sota-ES - Sotatercept in Patients With Congenital Heart Disease and Eisenmenger´s Syndrome
NCT01698567	Phase 1	TERMINATED	Antithrombin III in Infants With Cardiopulmonary Bypass (CPB)
NCT02549625	Phase 1	COMPLETED	Phase I Safety and Feasibility Study of Intracoronary Delivery of Autologous Bone Marrow Derived Mononuclear Cells
NCT03417999	Phase 1	TERMINATED	Pharmacokinetic Study of Intranasal Dexmedetomidine in Pediatric Patients With Congenital Heart Disease
NCT03946462	Phase 1	WITHDRAWN	Nitric Oxide During CPB to Reduce AKI in Neonates

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ROCK2 across ~30M SureChEMBL compounds — explore on Sugi Predict.