ROCK1

Summary

ROCK1 (Rho associated coiled-coil containing protein kinase 1, HGNC:10251) is a protein-coding gene on chromosome 18q11.1, encoding Rho-associated protein kinase 1 (Q13464). Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity.

This gene encodes a protein serine/threonine kinase that is activated when bound to the GTP-bound form of Rho. The small GTPase Rho regulates formation of focal adhesions and stress fibers of fibroblasts, as well as adhesion and aggregation of platelets and lymphocytes by shuttling between the inactive GDP-bound form and the active GTP-bound form. Rho is also essential in cytokinesis and plays a role in transcriptional activation by serum response factor. This protein, a downstream effector of Rho, phosphorylates and activates LIM kinase, which in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. A pseudogene, related to this gene, is also located on chromosome 18.

Source: NCBI Gene 6093 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 104 total
• Druggable target: yes — 49 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005406

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10251
Approved symbol	ROCK1
Name	Rho associated coiled-coil containing protein kinase 1
Location	18q11.1
Locus type	gene with protein product
Status	Approved
Aliases	p160ROCK
Ensembl gene	ENSG00000067900
Ensembl biotype	protein_coding
OMIM	601702
Entrez	6093

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 retained_intron, 2 protein_coding, 1 nonsense_mediated_decay

ENST00000399799, ENST00000578051, ENST00000582445, ENST00000583556, ENST00000584687, ENST00000584875, ENST00000635540

RefSeq mRNA: 1 — MANE Select: NM_005406 NM_005406

CCDS: CCDS11870

Canonical transcript exons

ENST00000399799 — 33 exons

Exon	Start	End
ENSE00000666550	21070532	21070613
ENSE00000666552	21049780	21049880
ENSE00000666554	21049092	21049229
ENSE00000666570	21023620	21023680
ENSE00000666572	21020151	21020239
ENSE00000666574	21015431	21015479
ENSE00000666578	21006699	21006790
ENSE00000666579	21006351	21006597
ENSE00000666582	20986950	20987110
ENSE00000666583	20984351	20984535
ENSE00000666584	20982763	20982832
ENSE00000948798	20992831	20992937
ENSE00000948799	20991176	20991326
ENSE00000948802	20969115	20969208
ENSE00000948803	20968772	20968860
ENSE00000948804	20967752	20967940
ENSE00001106113	20959840	20959928
ENSE00001106120	21008059	21008194
ENSE00001106127	21039472	21039563
ENSE00001106132	21042097	21042235
ENSE00001106143	20970348	20970513
ENSE00001106151	21042565	21042709
ENSE00001106157	21044102	21044186
ENSE00001106179	21045292	21045467
ENSE00001133053	20960136	20960206
ENSE00001133063	20966917	20967076
ENSE00001205106	21028776	21028935
ENSE00001540250	21110818	21111813
ENSE00001592636	20954783	20955044
ENSE00001652301	20953578	20953785
ENSE00001659208	20955167	20955245
ENSE00002580854	20946906	20951387
ENSE00003647279	20979910	20980004

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 97.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.6251 / max 365.2838, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171304	9.4677	1759
171303	7.6686	1741
171302	7.5492	1654
171301	4.9396	1424

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.78	gold quality
popliteal artery	UBERON:0002250	97.00	gold quality
tibial artery	UBERON:0007610	97.00	gold quality
monocyte	CL:0000576	95.83	gold quality
aorta	UBERON:0000947	95.72	gold quality
right coronary artery	UBERON:0001625	95.72	gold quality
leukocyte	CL:0000738	95.50	gold quality
bone marrow cell	CL:0002092	95.40	gold quality
left coronary artery	UBERON:0001626	95.33	gold quality
descending thoracic aorta	UBERON:0002345	94.84	gold quality
thoracic aorta	UBERON:0001515	94.72	gold quality
ascending aorta	UBERON:0001496	94.69	gold quality
colonic epithelium	UBERON:0000397	94.52	gold quality
mucosa of stomach	UBERON:0001199	94.41	gold quality
right lung	UBERON:0002167	94.41	gold quality
smooth muscle tissue	UBERON:0001135	94.16	gold quality
tibial nerve	UBERON:0001323	93.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.79	gold quality
vermiform appendix	UBERON:0001154	93.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.60	gold quality
lower esophagus	UBERON:0013473	93.54	gold quality
coronary artery	UBERON:0001621	92.74	gold quality
sural nerve	UBERON:0015488	92.35	gold quality
adrenal tissue	UBERON:0018303	92.33	gold quality
body of uterus	UBERON:0009853	92.23	gold quality
ventricular zone	UBERON:0003053	92.21	gold quality
upper lobe of left lung	UBERON:0008952	92.21	gold quality
gall bladder	UBERON:0002110	92.18	gold quality
left uterine tube	UBERON:0001303	92.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.03	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	11.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
ACTA2	Activation
BECN1	Activation
CASP3	Activation
CCN2	Activation
COL1A1	Activation
FGF2	Activation
LPP	Activation
MAPK14	Activation
NPPA	Activation

Upstream regulators (CollecTRI, top): APP, CTNNB1, DRAM2, FOXM1, GATA6, JUNB, LEF1, NFKB, ODAM, SP6, SUZ12, TCF21, TGFB2, TP53

miRNA regulators (miRDB)

137 targeting ROCK1, 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-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-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-539-5P	99.93	70.30	2855

Literature-anchored findings (GeneRIF, showing 40)

• role in the control of cell shape and lymphocyte chemotaxis (PMID:11751986)
• Expressed in myometrium (PMID:11818523)
• ROCK-1 may contribute to pancreatic cancer cell invasion and/or metastasis by facilitating cancer cell migration (PMID:11893932)
• ROCK and Dia have opposing effects on adherens junctions downstream of Rho (PMID:11992112)
• The Rho-associated protein kinase p160ROCK is required for centrosome positioning. (PMID:12034773)
• Activation of RhoA kinase promotes beta1 and beta2 integrin-dependent leukocyte de-adhesion by inhibiting cytoskeletal-dependent spreading, a new mechanism for regulation of integrin receptor avidity. (PMID:12193698)
• dual function in human parturition: in uterine muscle its expression and reversion contributes to contractions throughout labor; irreversible activation contributes to involution of uterus post-partum (PMID:12749591)
• Continued disruption of the cytoskeletal microtubule ring, appears to be a Rhokinase-dependent event involved in the transformation of discoid platelets into spheres. (PMID:12850840)
• Breast epithelial cells sense the rigidity or density of their environment via ROCK-mediated contractility and a subsequent down-regulation of Rho and FAK function, which is necessary for breast epithelial tubulogenesis to occur. (PMID:14610060)
• ROCKI interacts with the switch regions of RhoA (PMID:14660612)
• invasiveness of hepatocellular carcinoma is facilitated by the Rho/Rho-kinase pathway is likely to be relevant to tumor progression (PMID:14716844)
• 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)
• RhoA, mDia, and ROCK have roles in cell shape-dependent control of the Skp2-p27kip1 pathway and the G1/S transition (PMID:15096506)
• Potassium chloride acts in part through stimulation of Rho and ROCK, possibly secondary to voltage-dependent Ca2+ influx. (PMID:15208091)
• a novel nuclear export is activated by the ROCK signaling pathway to exclude hnRNP C1/C2 from nucleus, by which the compartmentalization of specific hnRNP components is disturbed in apoptotic c (PMID:15494373)
• epithelial cell motility is modulated by integrin engagment through RhoA/ROCK and PAK1 (PMID:15611088)
• data suggest that statins exert their effects on shedding of sAPP(alpha) from cultured cells, at least in part, by modulation of the isoprenoid pathway and ROCK1 (PMID:15647781)
• Enhanced activation of Rho kinase contributes to augmented contraction of the basilar artery to serotonin after subarachnoid hemorrhage. (PMID:15665056)
• Rho-kinase inhibition may be of value in treating age-related erectile dysfunction. (PMID:15713824)
• a Cdc42-MRCK signal mediates myosin-dependent cell motility and there is convergence between Rho and Cdc42 signalling (PMID:15723050)
• a pseudopodial-located RhoA/ROCK/p38/NHE1 signal module is regulated by Protein Kinase A gating and then regulates invasion in breast cancer cell lines (PMID:15843433)
• CD95 capping and the subsequent cellular polarization is a ROCK signaling-regulated process. (PMID:15855233)
• These results suggest that Rho-kinase regulates the association of alpha-adducin and spectrin with the actin cytoskeleton in platelet activation. (PMID:15910744)
• Hyperglycemia stimulates Rho-kinase activity via PKC- and oxidative stress-dependent pathways, leading to increased PAI-1 gene transcription (PMID:15956119)
• ROCK has a role in ischemia-induced endothelial dysfunction during stroke (PMID:16141422)
• two N-terminal regions interact to form a dimerization domain linking two kinase domains together (PMID:16249185)
• Our data suggested that p160ROCK was involved in ovarian cancer cell invasion and metastasis by facilitating cancer cell migration, and that p160ROCK might be a potential new effective target for preventing metastasis of ovarian cancer. (PMID:16371346)
• Prostate-derived sterile 20-like kinase 2 (PSK2) regulates apoptotic morphology via C-Jun N-terminal kinase and Rho kinase-1 (PMID:16407310)
• ERK-MAPK promotes endothelial cell survival and sprouting by downregulating Rho-kinase signaling. (PMID:16413470)
• there is an alternative mechanism for the hypoxic induction of VEGF in colon cancer that does not depend upon HIF-1alpha but instead requires the activation of PI3K/Rho/ROCK and c-Myc (PMID:16543245)
• Rho kinase, myosin-II, and p42/44 MAPK are potentially important players in different aspects of bile canalicular lumen morphogenesis. (PMID:16687572)
• A constitutively active dimeric human ROCK I (3-543) kinase domain was expressed in Sf-9 cells. We have identified a minimal functional subdomain of ROCK I that can be used in crystallization studies. (PMID:16712513)
• Vascular endothelial growth factor (VEGF) elicits the activation of the VEGFR2-ROCK pathway, leading to phosphorylation of Ser732 within FAK which changes the conformation of FAK, making it accessible to Pyk2. (PMID:16760434)
• Ability of MSCs to differentiate into neuron-like cells in response to CoCl(2), an effect that might act, in part, through HIF-1 activation and cell-cycle arrest, and which is potentiated by inhibition of ROCK. (PMID:16772336)
• burst in presteady-state kinetics & viscosity effect on k(cat) of 1.3 +/- 0.2 characterize phosphoryl transfer step to be fast & release of product &/or enzyme isomerization step accompanying it as rate-limiting at V(max) conditions. (PMID:16784244)
• cholesterol potentiates the Ca(2+) sensitization of VSM mediated by a SPC/Src-TK/Rho-kinase pathway (PMID:16825579)
• These results suggest that ROCK plays an essential role in the regulation of the intracellular mechanical response to VEGF of endothelial cells in a 3D matrix. (PMID:16891369)
• Data suggest that Rho kinase-dependent contractile force generation leads to co-alignment of cells and collagen fibrils along the plane of greatest resistance, and that this process contributes to global matrix contraction (PMID:16978606)
• ROCK-1-dependent caspase-3 activation was coupled with the activation of PTEN and the subsequent inhibition of protein kinase B (Akt) activity, all of which was attenuated by siRNA directed against ROCK-1 expression. (PMID:16983089)
• These results indicate that 2ME-induced barrier disruption is governed by microtubule depolymerization and p38- and ROCK-dependent mechanisms. (PMID:17012370)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rock1	ENSDARG00000058993
mus_musculus	Rock1	ENSMUSG00000024290
rattus_norvegicus	Rock1	ENSRNOG00000031092
drosophila_melanogaster	Rok	FBGN0026181
caenorhabditis_elegans	let-502	WBGENE00002694

Paralogs (5): CIT (ENSG00000122966), ROCK2 (ENSG00000134318), CDC42BPA (ENSG00000143776), CDC42BPG (ENSG00000171219), CDC42BPB (ENSG00000198752)

Protein

Protein identifiers

Rho-associated protein kinase 1 — Q13464 (reviewed: Q13464)

Alternative names: Renal carcinoma antigen NY-REN-35, Rho-associated, coiled-coil-containing protein kinase 1, Rho-associated, coiled-coil-containing protein kinase I, p160 ROCK-1

All UniProt accessions (3): Q13464, A0A0U1RQV4, J3KRH6

UniProt curated annotations — full annotation on UniProt →

Function. Protein kinase which is a key regulator of the 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 DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1. Promotes keratinocyte terminal differentiation. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles.

Subunit / interactions. Homodimer. Interacts with RHOB, RHOC, MYLC2B and PTEN. Interacts with ITGB1BP1 (via N-terminus and PTB domain). Interacts with RHOA (activated by GTP), CHORDC1, DAPK3, GEM, JIP3, RHOE, PPP1R12A, PFN1, LIMK1, LIMK2 and TSG101. Interacts with FHOD1 in a Src-dependent manner. Interacts with SHROOM3.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Golgi apparatus membrane. Cell projection. Bleb. Cell membrane. Lamellipodium. Ruffle.

Tissue specificity. Detected in blood platelets.

Post-translational modifications. Autophosphorylated on serine and threonine residues. Cleaved by caspase-3 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. The C-terminal auto-inhibitory domain interferes with kinase activity. RHOA binding leads to a conformation change and activation of the kinase. Truncated ROCK1 is constitutively activated.

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

RefSeq proteins (1): NP_005397* (*=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
IPR037310	ROCK1_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 (83 total): helix 27, strand 12, sequence variant 7, sequence conflict 7, region of interest 5, domain 5, modified residue 5, turn 4, coiled-coil region 2, binding site 2, initiator methionine 1, chain 1, compositionally biased region 1, active site 1, site 1, mutagenesis site 1, zinc finger region 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8P0S	X-RAY DIFFRACTION	2.2
3V8S	X-RAY DIFFRACTION	2.29
3O0Z	X-RAY DIFFRACTION	2.33
7S25	X-RAY DIFFRACTION	2.34
5WNF	X-RAY DIFFRACTION	2.45
4L2W	X-RAY DIFFRACTION	2.49
1S1C	X-RAY DIFFRACTION	2.6
2ETR	X-RAY DIFFRACTION	2.6
5WNE	X-RAY DIFFRACTION	2.6
7S26	X-RAY DIFFRACTION	2.74
3TV7	X-RAY DIFFRACTION	2.75
4W7P	X-RAY DIFFRACTION	2.8
5HVU	X-RAY DIFFRACTION	2.8
5KKT	X-RAY DIFFRACTION	2.8
3TWJ	X-RAY DIFFRACTION	2.9
5WNG	X-RAY DIFFRACTION	2.9
5BML	X-RAY DIFFRACTION	2.95
2ETK	X-RAY DIFFRACTION	2.96
6E9W	X-RAY DIFFRACTION	2.96
3NCZ	X-RAY DIFFRACTION	3
5WNH	X-RAY DIFFRACTION	3.1
2ESM	X-RAY DIFFRACTION	3.2
4YVC	X-RAY DIFFRACTION	3.2
3D9V	X-RAY DIFFRACTION	3.3
3NDM	X-RAY DIFFRACTION	3.3
5KKS	X-RAY DIFFRACTION	3.3
5UZJ	X-RAY DIFFRACTION	3.3
7JOU	X-RAY DIFFRACTION	3.32
4YVE	X-RAY DIFFRACTION	3.4
5F5P	X-RAY DIFFRACTION	3.57

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13464-F1	76.42	0.28

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): 198 (proton acceptor); 1113–1114 (cleavage; by caspase-3)

Ligand- & substrate-binding residues (2): 82–90; 105

Post-translational modifications (5): 2, 647, 1105, 1108, 1328

Mutagenesis-validated functional residues (1):

Position	Phenotype
1113	abolishes cleavage by caspase-3.

Function

Pathways and Gene Ontology

Reactome pathways

40 pathways

ID	Pathway
R-HSA-111465	Apoptotic cleavage of cellular proteins
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-6798695	Neutrophil degranulation
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-9696264	RND3 GTPase cycle
R-HSA-109581	Apoptosis
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
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

MSigDB gene sets: 567 (showing top): BIOCARTA_RHO_PATHWAY, GOBP_MITOTIC_CYTOKINESIS, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_PROTEIN_BINDING, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CIRCULATORY_SYSTEM_PROCESS

GO Biological Process (65): mitotic cytokinesis (GO:0000281), epithelial to mesenchymal transition (GO:0001837), aortic valve morphogenesis (GO:0003180), apical constriction (GO:0003383), smooth muscle contraction (GO:0006939), leukocyte cell-cell adhesion (GO:0007159), signal transduction (GO:0007165), Rho protein signal transduction (GO:0007266), positive regulation of autophagy (GO:0010508), positive regulation of cardiac muscle hypertrophy (GO:0010613), positive regulation of gene expression (GO:0010628), negative regulation of angiogenesis (GO:0016525), peptidyl-serine phosphorylation (GO:0018105), membrane to membrane docking (GO:0022614), actin cytoskeleton organization (GO:0030036), regulation of cell adhesion (GO:0030155), regulation of cell migration (GO:0030334), cortical actin cytoskeleton organization (GO:0030866), actomyosin structure organization (GO:0031032), neuron projection development (GO:0031175), bleb assembly (GO:0032060), negative regulation of protein binding (GO:0032091), regulation of actin cytoskeleton organization (GO:0032956), intracellular signal transduction (GO:0035556), positive regulation of MAPK cascade (GO:0043410), regulation of keratinocyte differentiation (GO:0045616), regulation of neuron differentiation (GO:0045664), embryonic morphogenesis (GO:0048598), leukocyte migration (GO:0050900), leukocyte tethering or rolling (GO:0050901), negative regulation of membrane protein ectodomain proteolysis (GO:0051045), myoblast migration (GO:0051451), regulation of stress fiber assembly (GO:0051492), regulation of focal adhesion assembly (GO:0051893), positive regulation of focal adhesion assembly (GO:0051894), mRNA destabilization (GO:0061157), negative regulation of biomineral tissue development (GO:0070168), regulation of microtubule cytoskeleton organization (GO:0070507), response to transforming growth factor beta (GO:0071559), protein localization to plasma membrane (GO:0072659)

GO Molecular Function (14): protein serine/threonine kinase activity (GO:0004674), 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), 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 (16): Golgi membrane (GO:0000139), ruffle (GO:0001726), extracellular region (GO:0005576), cytoplasm (GO:0005737), centriole (GO:0005814), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cytoplasmic stress granule (GO:0010494), lamellipodium (GO:0030027), bleb (GO:0032059), secretory granule lumen (GO:0034774), Schaffer collateral - CA1 synapse (GO:0098685), Golgi apparatus (GO:0005794), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
RHO GTPase cycle	5
EPH-Ephrin signaling	2
Apoptotic execution phase	1
GPCR downstream signalling	1
Sema4D in semaphorin signaling	1
Signaling by VEGF	1
RHO GTPase Effectors	1
Innate Immune System	1
RHOBTB GTPase Cycle	1
SARS-CoV Infections	1
Programmed Cell Death	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
plasma membrane bounded cell projection	3
regulation of cellular process	2
actin cytoskeleton organization	2
protein kinase activity	2
protein serine/threonine kinase activity	2
cell leading edge	2
intracellular membraneless organelle	2
cytoplasm	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
mesenchymal cell differentiation	1
aortic valve development	1
heart valve morphogenesis	1
epithelial cell morphogenesis	1
actin-mediated cell contraction	1
muscle contraction	1
cell-cell adhesion	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
small GTPase-mediated signal transduction	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
positive regulation of muscle hypertrophy	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
protein phosphorylation	1
peptidyl-serine modification	1
membrane docking	1
cytoskeleton organization	1

Protein interactions and networks

STRING

4713 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ROCK1	RHOA	P06749	998
ROCK1	RND3	P52199	977
ROCK1	PPP1R12A	O14974	839
ROCK1	RHOC	P08134	821
ROCK1	CFL1	P23528	794
ROCK1	CFL2	Q9Y281	791
ROCK1	RHOB	P01121	779
ROCK1	CDC42	P21181	757
ROCK1	MYC	P01106	723
ROCK1	TSG101	Q99816	719
ROCK1	CASP3	P42574	714
ROCK1	APEX1	P27695	685
ROCK1	ARHGAP35	Q9NRY4	683
ROCK1	CTNND1	O60716	666
ROCK1	HIF1A	Q16665	643

IntAct

89 interactions, top by confidence:

A	B	Type	Score
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
ROCK1	MAGEB4	psi-mi:“MI:0915”(physical association)	0.740
MAGEB4	ROCK1	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ROCK1	RHOA	psi-mi:“MI:0407”(direct interaction)	0.660
ROCK1	RHOA	psi-mi:“MI:0915”(physical association)	0.660
DCAF7	PFDN6	psi-mi:“MI:0914”(association)	0.570
LMO2	ROCK1	psi-mi:“MI:0915”(physical association)	0.560
FAM124A	ROCK1	psi-mi:“MI:0915”(physical association)	0.560
ROCK1	CFAP206	psi-mi:“MI:0915”(physical association)	0.560
POLR3C	ROCK1	psi-mi:“MI:0915”(physical association)	0.560
ROCK1	FAM124A	psi-mi:“MI:0915”(physical association)	0.560
CFAP206	ROCK1	psi-mi:“MI:0915”(physical association)	0.560
ROCK1	POLR3C	psi-mi:“MI:0915”(physical association)	0.560
ROCK1	LMO2	psi-mi:“MI:0915”(physical association)	0.560
MYBPH	ROCK1	psi-mi:“MI:0407”(direct interaction)	0.540
MYBPH	ROCK1	psi-mi:“MI:0915”(physical association)	0.540
IL20RA	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
MAGEB4	MAGEA1	psi-mi:“MI:0914”(association)	0.530
ATP6V0A1	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
ROCK1	FRMD5	psi-mi:“MI:0915”(physical association)	0.520
FRMD5	ROCK1	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (212): ROCK1 (Two-hybrid), ROCK1 (Two-hybrid), POLR3C (Two-hybrid), C6orf165 (Two-hybrid), FAM124A (Two-hybrid), ROCK1 (Affinity Capture-RNA), ROCK1 (Affinity Capture-MS), ROCK1 (Affinity Capture-MS), ROCK1 (Affinity Capture-MS), ROCK1 (Affinity Capture-MS), ROCK1 (Affinity Capture-MS), ROCK1 (Affinity Capture-MS), ROCK1 (Affinity Capture-MS), ROCK1 (Affinity Capture-MS), ROCK1 (PCA)

ESM2 similar proteins: B0WPU9, B2GUE2, B3MNR6, B3NL60, B4G831, B4I5P7, B4JAL5, B4KE73, B4N1C2, B4PAF2, B4Q9E6, B6MFW3, F1MA98, F6ZDS4, O15078, O61493, O77819, P12270, P16568, P61584, P70335, P70403, P85001, P85120, Q08C53, Q13464, Q17AF4, Q24185, Q29N92, Q2T9W6, Q3UU96, Q5EE04, Q5RG45, Q5TZ80, Q5ZJ27, Q5ZKK5, Q63644, Q66GS9, Q6A078, Q6GQ73

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

82 interactions.

A	Effect	B	Mechanism
CASP3	up-regulates	ROCK1	cleavage
ROCK1	up-regulates	Membrane_blebbing
ROCK1	up-regulates	MYLK	binding
ROCK1	“up-regulates activity”	MAPK8	phosphorylation
ROCK1	up-regulates	MAPK8IP3	phosphorylation
ROCK1	up-regulates	RND3	phosphorylation
ROCK1	up-regulates	PTEN	phosphorylation
ROCK1	up-regulates	ARHGAP24	phosphorylation
ROCK1	down-regulates	MPRIP	phosphorylation
ROCK1	up-regulates	FHOD1	phosphorylation
ROCK1	up-regulates	SOX9	phosphorylation
ROCK1	down-regulates	KCNK3	phosphorylation
ROCK1	“up-regulates activity”	KCNK3	phosphorylation
ROCK1	down-regulates	ARHGAP35	phosphorylation
ROCK1	up-regulates	EZR	phosphorylation
RHOA	“up-regulates activity”	ROCK1	binding
ROCK1	down-regulates	PFN1	phosphorylation
ROCK1	“up-regulates quantity by expression”	LPP	“transcriptional regulation”
ROCK1	down-regulates	PPP1R12B	phosphorylation
ROCK1	up-regulates	Brown_adipogenesis
Y-27632	down-regulates	ROCK1	“chemical inhibition”
ROCK1	unknown	DES	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4338 predictions. Top by Δscore:

Variant	Effect	Δscore
18:20951266:AAC:A	donor_gain	1.0000
18:20951267:A:C	donor_gain	1.0000
18:20953782:CTTA:C	acceptor_gain	1.0000
18:20953783:TTA:T	acceptor_gain	1.0000
18:20953784:TA:T	acceptor_gain	1.0000
18:20953786:C:CC	acceptor_gain	1.0000
18:20953786:CT:C	acceptor_loss	1.0000
18:20953788:A:AC	acceptor_gain	1.0000
18:20953791:T:C	acceptor_gain	1.0000
18:20953791:T:TC	acceptor_gain	1.0000
18:20955161:TTTTA:T	donor_loss	1.0000
18:20955162:TTTAC:T	donor_loss	1.0000
18:20955163:TTAC:T	donor_loss	1.0000
18:20955164:TAC:T	donor_loss	1.0000
18:20955165:A:T	donor_loss	1.0000
18:20955166:C:A	donor_loss	1.0000
18:20955241:GTTTA:G	acceptor_gain	1.0000
18:20955242:TTTA:T	acceptor_gain	1.0000
18:20955243:TTA:T	acceptor_gain	1.0000
18:20955243:TTAC:T	acceptor_loss	1.0000
18:20955244:TA:T	acceptor_gain	1.0000
18:20955244:TACTA:T	acceptor_loss	1.0000
18:20955246:C:CC	acceptor_gain	1.0000
18:20955246:CTA:C	acceptor_loss	1.0000
18:20959838:A:AC	donor_gain	1.0000
18:20959839:C:CA	donor_gain	1.0000
18:20959839:CT:C	donor_gain	1.0000
18:20959839:CTCT:C	donor_gain	1.0000
18:20959924:ACATA:A	acceptor_gain	1.0000
18:20959925:CATA:C	acceptor_gain	1.0000

AlphaMissense

9063 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:20953715:C:A	W1308C	1.000
18:20953715:C:G	W1308C	1.000
18:20953717:A:G	W1308R	1.000
18:20953717:A:T	W1308R	1.000
18:20954787:A:C	C1283W	1.000
18:20954788:C:T	C1283Y	1.000
18:20954789:A:G	C1283R	1.000
18:20954845:C:G	C1264S	1.000
18:20954846:A:G	C1264R	1.000
18:20954846:A:T	C1264S	1.000
18:20954853:A:C	C1261W	1.000
18:20954854:C:G	C1261S	1.000
18:20954855:A:G	C1261R	1.000
18:20954855:A:T	C1261S	1.000
18:20954863:G:T	A1258D	1.000
18:20954903:A:G	C1245R	1.000
18:20954910:A:C	C1242W	1.000
18:20954911:C:G	C1242S	1.000
18:20954911:C:T	C1242Y	1.000
18:20954912:A:G	C1242R	1.000
18:20954912:A:T	C1242S	1.000
18:20954944:A:G	F1231S	1.000
18:20955038:A:C	Y1200D	1.000
18:20955040:A:G	L1199P	1.000
18:20955171:A:G	F1196S	1.000
18:20955174:A:T	I1195K	1.000
18:20955222:A:T	V1179E	1.000
18:20955231:A:T	V1176D	1.000
18:20955240:A:G	L1173P	1.000
18:20959849:A:G	L1168S	1.000

dbSNP variants (sampled 300 via entrez): RS1000051907 (18:20962032 A>G), RS1000097379 (18:21091668 G>A), RS1000186881 (18:20980212 G>A), RS1000187687 (18:21105184 A>G), RS1000198803 (18:20973572 C>T), RS1000222833 (18:21071176 T>C), RS1000272020 (18:21110406 C>G,T), RS1000292042 (18:21064058 T>G), RS1000311154 (18:21018497 T>TC), RS1000326903 (18:21038551 C>T), RS1000451860 (18:21058064 G>C), RS1000455272 (18:21070870 C>T), RS1000465541 (18:21025055 A>G), RS1000491021 (18:21000142 G>T), RS1000500236 (18:21005142 T>C)

Disease associations

OMIM: gene MIM:601702 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST006485_11	Telomere length	2.000000e-06
GCST007100_11	Asthma exacerbations in inhaled corticosteroid treatment	3.000000e-06
GCST008925_10	Lysophosphatidylcholine levels	2.000000e-10
GCST008925_11	Lysophosphatidylcholine levels	3.000000e-08
GCST008925_2	Lysophosphatidylcholine levels	2.000000e-10
GCST008925_3	Lysophosphatidylcholine levels	2.000000e-10
GCST008925_4	Lysophosphatidylcholine levels	2.000000e-10
GCST008925_5	Lysophosphatidylcholine levels	2.000000e-09
GCST008925_6	Lysophosphatidylcholine levels	4.000000e-10
GCST008925_7	Lysophosphatidylcholine levels	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007614	asthma exacerbation measurement
EFO:0010224	lysophosphatidylcholine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111459 (PROTEIN FAMILY), CHEMBL3231 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

49 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 209,005 (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
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
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	870
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL541388	FASUDIL HYDROCHLORIDE	2
CHEMBL1090090	VX-702	2
CHEMBL1667969	SAR-407899 FREE BASE	2
CHEMBL1721885	SU-014813	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL1967878	CENISERTIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL1980715	LAUROGUADINE	2
CHEMBL3039513	DECERNOTINIB	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 (18 total), top 18:

Ligand	Action	Affinity	Parameter
compound 8 [PMID: 25898023]	Inhibition	9.0	pIC50
RKI-1447	Inhibition	9.0	pIC50
GSK269962A	Inhibition	8.8	pIC50
HSD1590	Inhibition	8.78	pKd
ROCK inhibitor 3	Inhibition	8.0	pIC50
compound 35 [PMID: 20684608]	Inhibition	8.0	pIC50
GSK180736A	Inhibition	7.85	pIC50
GSK429286A	Inhibition	7.85	pIC50
netarsudil	Inhibition	7.49	pIC50
compound 22 [PMID: 20462760]	Inhibition	7.41	pIC50
ripasudil	Inhibition	7.29	pIC50
compound 33 [PMID: 19364658]	Inhibition	7.22	pIC50
compound E22 [PMID: 31298542]	Inhibition	7.19	pIC50
ninvosudil	Inhibition	6.85	pKi
cortistatin A	Inhibition	6.6	pKd
SAR407899	Inhibition	6.56	pIC50
fasudil	Inhibition	5.57	pIC50
belumosudil	Inhibition	4.62	pIC50

Binding affinities (BindingDB)

1070 measured of 1596 human assays (1599 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Preparation of (2R)-2-amino-2-(3-methoxyphenyl)-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]acetamide	IC50	0.18 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
(2S)-3-amino-2-benzyl-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]propanamide	IC50	0.18 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-cyclohexylpropanamide	IC50	0.19 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
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
Preparation of (2S)-2-amino-2-phenyl-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]acetamide	IC50	0.24 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
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
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-(m-tolyl)propanamide	IC50	0.29 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-(3-methoxyphenyl)propanamide	IC50	0.3 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
3-(1-((3-(1H-pyrazol-4-yl)-1H-indol-7-yl)amino)-3-amino-1-oxopropan-2-yl)benzyl methylcarbamate	IC50	0.32 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-(4-(hydroxymethyl)phenyl)propanamide	IC50	0.33 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
US20250346616, Example 40	IC50	0.33 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-(3-hydroxyphenyl)propanamide	IC50	0.37 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
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
3-amino-2-(4-aminophenyl)-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]propanamide	IC50	0.39 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
2-[4-(2-aminoethyl) piperazin-1-yl]-2-phenyl-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]acetamide	IC50	0.42 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
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-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-(5-methylpyridin-3-yl)propanamide	IC50	0.43 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-(4-methylpiperazin-1-yl)-2-phenylpropanamide	IC50	0.44 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-2-(1-methylpiperidin-4-yl)-2-phenylacetamide	IC50	0.53 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-(pyridin-3-yl)propanamide	IC50	0.55 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-(4-(hydroxymethyl)phenyl)propanamide	IC50	0.59 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(2-amino-1-(3-methoxyphenyl)ethyl)-3-(1H-pyrazol-4-yl)-1H-indole-7-carboxamide	IC50	0.62 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-(4-methylpiperazin-1-yl)-2-phenylpropanamide	IC50	0.71 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-2-amino-2-(pyridin-3-yl)acetamide	IC50	0.76 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-[(1S)-2-amino-1-phenylethyl]-3-methoxy-4-pyrazolidin-4-ylbenzamide	IC50	0.77 nM	US-9458110: Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
3-amino-2-(4-fluorophenyl)-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]propanamide	IC50	0.81 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-(3-methoxyphenyl)propanamide	IC50	0.84 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-[(3-hydroxyphenyl)methyl]-3-methoxy-4-pyrazolidin-4-ylbenzamide	IC50	0.85 nM	US-9458110: Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
3-(1-((3-(1H-pyrazol-4-yl)-1H-indol-7-yl)amino)-3-amino-1-oxopropan-2-yl)benzyl methylcarbamate	IC50	0.86 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(1-amino-3-phenylpropan-2-yl)-3-(1H-pyrazol-4-yl)-1H-indole-7-carboxamide	IC50	0.88 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
3-amino-2-benzyl-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]propenamide	IC50	0.93 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
Preparation of (2S)-3-amino-2-phenyl-N-[7-(1H-pyrazol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl]propanamide	IC50	0.96 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(1-amino-3-phenylpropan-2-yl)-3-methoxy-4-pyrazolidin-4-ylbenzamide	IC50	1.04 nM	US-9458110: Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
3-amino-2-cyclohexyl-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]propanamide	IC50	1.1 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
3-methoxy-N-[(1R)-1-(3-methoxyphenyl)ethyl]-4-pyrazolidin-4-ylbenzamide	IC50	1.11 nM	US-9458110: Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-(pyridin-3-yl)propanamide	IC50	1.2 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
3-amino-2-(3-chlorophenyl)-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]propanamide	IC50	1.2 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
3-amino-2-(oxan-3-yl)-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]propanamide	IC50	1.2 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
2-methoxy-N-[[3-[(1-methylpiperidin-4-yl)carbamoyl]phenyl]methyl]-4-pyrazolidin-4-ylbenzamide	IC50	1.24 nM	US-9458110: Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-2-(1-methylpiperidin-4-yl)-2-phenylacetamide	IC50	1.3 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
3-amino-2-(2-methoxyphenyl)-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]propanamide	IC50	1.3 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
3-amino-2-(5-methoxypyridin-3-yl)-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]propanamide	IC50	1.3 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
4-(1-((3-(1H-pyrazol-4-yl)-1H-indol-7-yl)amino)-3-amino-1-oxopropan-2-yl)benzamide	IC50	1.3 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
Preparation of(S)—N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-phenylpropanamide	IC50	1.4 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-(3-(1H-pyrazol-4-yl)-1H-indol-7-yl)-3-amino-2-(tetrahydro-2H-pyran-4-yl)propanamide	IC50	1.4 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
3-amino-2-(1-methyl-2-oxopyridin-4-yl)-N-[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]propanamide	IC50	1.4 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF
N-[(1R)-1-[3-(cyclopentylcarbamoyl)phenyl]ethyl]-2-ethoxy-4-(1H-pyrazol-4-yl)benzamide	IC50	1.51 nM	US-10738007: Amide compounds as kinase inhibitors, compositions and methods of treatment
N-[3-(dimethylamino)-1-phenylpropyl]-3-methoxy-4-(1H-pyrazol-4-yl)benzamide	IC50	1.53 nM	US-9458110: Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
N-[[3-[(1-ethylpyrrolidin-2-yl)methylcarbamoyl]phenyl]methyl]-3-methoxy-4-(1H-pyrazol-4-yl)benzamide	IC50	1.54 nM	US-9458110: Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
[4-[(1S)-1-(aminomethyl)-2-oxo-2-[[3-(1H-pyrazol-4-yl)-1H-indol-7-yl]amino]ethyl]phenyl]methyl 6-nitrooxyhexanoate	IC50	1.6 nM	US-20250346616: ROCK INHIBITORS AND USES THEREOF

ChEMBL bioactivities

3188 potent at pChembl≥5 of 3442 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.82	Ki	0.15	nM	CHEMBL6169753
9.70	IC50	0.2	nM	CHEMBL4107027
9.70	Ki	0.2	nM	NETARSUDIL-M1
9.70	IC50	0.2	nM	CHEMBL5901861
9.59	IC50	0.26	nM	CHEMBL3902471
9.55	Ki	0.28	nM	CHEMBL6175959
9.55	Kd	0.28	nM	STAUROSPORINE
9.41	IC50	0.39	nM	CHEMBL3961538
9.40	IC50	0.4	nM	CHEMBL5987641
9.40	IC50	0.4	nM	CHEMBL5739910
9.38	Ki	0.42	nM	CHEMBL6161530
9.37	IC50	0.43	nM	CHEMBL3949136
9.35	IC50	0.444	nM	STAUROSPORINE
9.35	Ki	0.448	nM	CHEMBL5743382
9.31	IC50	0.49	nM	CHEMBL4763198
9.30	IC50	0.5	nM	CHEMBL5756060
9.28	IC50	0.53	nM	CHEMBL3218297
9.22	IC50	0.6	nM	BAY-549
9.20	IC50	0.63	nM	CHEMBL3578252
9.19	IC50	0.64	nM	STAUROSPORINE
9.17	IC50	0.68	nM	STAUROSPORINE
9.17	IC50	0.67	nM	CHEMBL3578252
9.11	IC50	0.77	nM	CHEMBL4114628
9.10	IC50	0.799	nM	STAUROSPORINE
9.10	IC50	0.8	nM	CHEMBL4114628
9.10	IC50	0.8	nM	CHEMBL4791701
9.10	Ki	0.7943	nM	CHEMBL1971606
9.10	Ki	0.7943	nM	CHEMBL1980995
9.10	Ki	0.7943	nM	CHEMBL1870106
9.07	IC50	0.85	nM	CHEMBL3986802
9.05	IC50	0.9	nM	CHEMBL3913336
9.00	IC50	1	nM	CHEMBL2333898
9.00	IC50	1	nM	CHEMBL4448806
9.00	Ki	1	nM	CHEMBL4796289
9.00	Ki	1	nM	CHEMBL4777515
9.00	Ki	1	nM	NETARSUDIL
9.00	IC50	1	nM	CHEMBL3913336
8.98	IC50	1.04	nM	CHEMBL3964418
8.96	IC50	1.11	nM	CHEMBL3913336
8.96	IC50	1.1	nM	STAUROSPORINE
8.92	IC50	1.2	nM	CHEMBL3770836
8.92	IC50	1.2	nM	CHEMBL4747999
8.92	IC50	1.2	nM	CHEMBL4785041
8.91	IC50	1.24	nM	CHEMBL3925017
8.91	IC50	1.22	nM	CHEMBL4461288
8.91	IC50	1.22	nM	CHEMBL5287991
8.90	IC50	1.26	nM	CHEMBL5619410
8.90	IC50	1.26	nM	STAUROSPORINE
8.90	Ki	1.259	nM	CHEMBL1969151
8.90	Ki	1.259	nM	CHEMBL1994724

PubChem BioAssay actives

1245 with measured affinity, of 3792 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)-3-amino-2-[4-(hydroxymethyl)phenyl]-N-isoquinolin-6-ylpropanamide	1674172: Inhibition of human ROCK1 expressed in baculovirus expression system by Kinase-Glo luminescent Assay	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	625015: Binding constant for ROCK1 kinase domain	kd	0.0003	uM
N-[(1R)-1-(3-methoxyphenyl)ethyl]-6-methyl-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1675419: Inhibition of ROCK1 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH as substrate by caliper assay	ic50	0.0005	uM
1-[(3-hydroxyphenyl)methyl]-3-(4-pyridin-4-yl-1,3-thiazol-2-yl)urea;methanesulfonic acid	1119751: Inhibition of ROCK1 (unknown origin)	ic50	0.0005	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	1925397: Inhibition of ROCK1 (unknown origin)	ic50	0.0006	uM
6-ethyl-N-[(1R)-1-(3-methoxyphenyl)ethyl]-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1675419: Inhibition of ROCK1 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH as substrate by caliper assay	ic50	0.0006	uM
3-ethyl-N-[(1R)-1-(3-methoxyphenyl)ethyl]-4-(1H-pyrazol-4-yl)benzamide	1675402: Inhibition of ROCK1 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH peptide substrate by caliper assay	ic50	0.0008	uM
N-[(1S)-2-amino-1-phenylethyl]-3-methoxy-4-(1H-pyrazol-4-yl)benzamide	1675402: Inhibition of ROCK1 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH peptide substrate by caliper assay	ic50	0.0008	uM
3-methoxy-N-[(1R)-1-(3-methoxyphenyl)ethyl]-4-(1H-pyrazol-4-yl)benzamide	1675402: Inhibition of ROCK1 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH peptide substrate by caliper assay	ic50	0.0009	uM
2-[3-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3-thiazol-2-yl]acetamide	1398834: Inhibition of ROCK1 (6 to 553 residues) (unknown origin) using Lys-Lys-Arg-Asn-Arg-Thr-Leu-Ser-Val as substrate in presence of ATP by spectrophotometric assay	ki	0.0010	uM
2-[(3S,4R)-4-(4-chlorophenyl)pyrrolidin-3-yl]-6-(1H-pyrazol-4-yl)-3H-quinazolin-4-one	731247: Inhibition of ROCK1 (unknown origin)	ic50	0.0010	uM
N-[(4-chlorophenyl)-[4-oxo-6-(1H-pyrazol-4-yl)-3H-quinazolin-2-yl]methyl]-2-(dimethylamino)acetamide	731247: Inhibition of ROCK1 (unknown origin)	ic50	0.0010	uM
N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]-4-morpholin-4-ylbenzamide	1797145: ROCK 1 Kinase Activity Assay from Article 10.1021/jm060873p: “Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity.”	ic50	0.0010	uM
N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]-4-[(dimethylamino)methyl]benzamide	1797145: ROCK 1 Kinase Activity Assay from Article 10.1021/jm060873p: “Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity.”	ic50	0.0010	uM
N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]-4-[2-(dimethylamino)ethoxy]benzamide	1797145: ROCK 1 Kinase Activity Assay from Article 10.1021/jm060873p: “Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity.”	ic50	0.0010	uM
4-(aminomethyl)-N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]benzamide	1797145: ROCK 1 Kinase Activity Assay from Article 10.1021/jm060873p: “Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity.”	ic50	0.0010	uM
N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]-4-(morpholin-4-ylmethyl)benzamide	1797145: ROCK 1 Kinase Activity Assay from Article 10.1021/jm060873p: “Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity.”	ic50	0.0010	uM
N-[(1R)-1-(3-methoxyphenyl)ethyl]-4-pyridin-4-ylbenzamide	1531984: Inhibition of ROCK1 (unknown origin) incubated for 2 hrs by AbbVie kinase panel assay	ic50	0.0010	uM
N-[(3-methoxyphenyl)methyl]-6-(1H-pyrazol-4-yl)-1H-indole-3-carboxamide	631998: Inhibition of ROCK1	ic50	0.0010	uM
N-[(3-methoxyphenyl)methyl]-1-methyl-6-(1H-pyrazol-4-yl)pyrrolo[2,3-b]pyridine-3-carboxamide	631998: Inhibition of ROCK1	ic50	0.0010	uM
N-[(3-methoxyphenyl)methyl]-1-methyl-6-(1H-pyrazol-4-yl)indole-3-carboxamide	631998: Inhibition of ROCK1	ic50	0.0010	uM
2-[3-(ethylsulfonylamino)phenyl]-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3-thiazol-2-yl]acetamide	1398834: Inhibition of ROCK1 (6 to 553 residues) (unknown origin) using Lys-Lys-Arg-Asn-Arg-Thr-Leu-Ser-Val as substrate in presence of ATP by spectrophotometric assay	ki	0.0010	uM
N-[4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3-thiazol-2-yl]-2-[3-(3-piperidin-4-ylpropoxy)phenyl]acetamide	1683778: Inhibition of ROCK1 (unknown origin)	ki	0.0010	uM
[4-[(2S)-3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 2,4-dimethylbenzoate;dihydrochloride	1675423: Inhibition of recombinant human GST-tagged ROCK1 catalytic domain expressed in baculovirus expression system by Kinase-Glo luminescent kinase assay	ki	0.0010	uM
Netarsudil	1894030: Inhibition of ROCK1 (unknown origin)	ki	0.0010	uM
methyl 4-[[3-[2-(aminomethyl)-5-[(3-fluoro-4-pyridinyl)carbamoyl]phenyl]benzoyl]amino]benzoate	1206559: Inhibition of human N-terminal GST-tagged ROCK1 expressed in insect cells using long S6 kinase peptide as substrate by radiometric assay in presence of [32P]ATP	ic50	0.0010	uM
methyl 2-[4-[[3-[2-(aminomethyl)-5-[(3-fluoro-4-pyridinyl)carbamoyl]phenyl]benzoyl]amino]phenyl]acetate	1206559: Inhibition of human N-terminal GST-tagged ROCK1 expressed in insect cells using long S6 kinase peptide as substrate by radiometric assay in presence of [32P]ATP	ic50	0.0010	uM
methyl 3-[[3-[2-(aminomethyl)-5-[(3-fluoro-4-pyridinyl)carbamoyl]phenyl]benzoyl]amino]benzoate	1206559: Inhibition of human N-terminal GST-tagged ROCK1 expressed in insect cells using long S6 kinase peptide as substrate by radiometric assay in presence of [32P]ATP	ic50	0.0010	uM
methyl 2-[3-[[3-[2-(aminomethyl)-5-[(3-fluoro-4-pyridinyl)carbamoyl]phenyl]benzoyl]amino]phenyl]acetate	1206559: Inhibition of human N-terminal GST-tagged ROCK1 expressed in insect cells using long S6 kinase peptide as substrate by radiometric assay in presence of [32P]ATP	ic50	0.0010	uM
N-[(1R)-1-(3-methoxyphenyl)ethyl]-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1675419: Inhibition of ROCK1 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH as substrate by caliper assay	ic50	0.0012	uM
N-[[3-[[(2S)-1-ethylpyrrolidin-2-yl]methylcarbamoyl]phenyl]methyl]-6-methyl-6H-isochromeno[3,4-c]pyridine-8-carboxamide	1675419: Inhibition of ROCK1 (unknown origin) using FITC-AHA-AKRRRLSSLRA-OH as substrate by caliper assay	ic50	0.0012	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	1564121: Inhibition of human ROCK1 using KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK as substrate incubated for 20 mins in presence of [gamma33P]ATP by filter binding method	ic50	0.0012	uM
[2-methoxy-3-(3H-pyrazolo[4,5-f]quinolin-7-yl)phenyl]boronic acid	1925397: Inhibition of ROCK1 (unknown origin)	ic50	0.0012	uM
3-amino-N-isoquinolin-6-yl-2-phenylpropanamide	1280088: Inhibition of ROCK1 (unknown origin)	ic50	0.0012	uM
[4-[(2S)-3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 3-(nitrooxymethyl)benzoate;methanesulfonic acid	2129254: Inhibition of ROCK1 (unknown origin) incubated for 10 mins in presence of ATP by mobility shift assay	ic50	0.0013	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	659383: Binding affinity to His6-tagged recombinant human ROCK1 by fluorescence anisotropy assay	kd	0.0013	uM
3-benzyl-2,2-dimethyl-6-pyridin-4-yl-1H-thieno[3,2-d]pyrimidin-4-one	1364443: Inhibition of recombinant human N-terminal GST-tagged ROCK1 (1 to 477 residues) expressed in baculovirus expression system using biotin-STK substrate-2 as substrate preincubated for 5 mins followed by ATP addition after 2 hrs by TR-FRET assay	ic50	0.0015	uM
[4-[3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 4-(nitrooxymethyl)benzoate;methanesulfonic acid	2129254: Inhibition of ROCK1 (unknown origin) incubated for 10 mins in presence of ATP by mobility shift assay	ic50	0.0015	uM
N-[4-(1H-pyrazol-4-yl)phenyl]-2,3-dihydro-1,4-benzodioxine-3-carboxamide	1579930: Inhibition of human ROCK incubated for 20 mins followed by 33P ATP after 120 mins	ic50	0.0015	uM
N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]-4-(2-morpholin-4-ylethoxy)benzamide	1564132: Inhibition of N-terminal His-tagged human ROCK1 (3 to 543 residues) expressed in baculovirus infected Sf9 cells using biotin-Ahx-AKRRRLSSLRA-CONH2 as substrate incubated for 90 mins in presence of [gamma33P]ATP by scintillation counting method	ic50	0.0016	uM
N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]acetamide	1797145: ROCK 1 Kinase Activity Assay from Article 10.1021/jm060873p: “Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity.”	ic50	0.0018	uM
2-[3-(2-methoxyethylsulfamoyl)phenyl]-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3-thiazol-2-yl]acetamide	1398834: Inhibition of ROCK1 (6 to 553 residues) (unknown origin) using Lys-Lys-Arg-Asn-Arg-Thr-Leu-Ser-Val as substrate in presence of ATP by spectrophotometric assay	ki	0.0020	uM
4-(4-chloro-2-fluorophenyl)-N-(1H-indazol-5-yl)-2-(2-methoxy-4-pyridinyl)-6-methyl-1,4-dihydropyrimidine-5-carboxamide	1798562: ROCK Kinase Inhibition Assay from Article 10.1021/jm8005096: “Potent, selective and orally bioavailable dihydropyrimidine inhibitors of Rho kinase (ROCK1) as potential therapeutic agents for cardiovascular diseases.”	ic50	0.0020	uM
2-[3-(methanesulfonamido)phenyl]-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3-thiazol-2-yl]acetamide	1398834: Inhibition of ROCK1 (6 to 553 residues) (unknown origin) using Lys-Lys-Arg-Asn-Arg-Thr-Leu-Ser-Val as substrate in presence of ATP by spectrophotometric assay	ki	0.0020	uM
2-[(3S,4R)-4-phenylpyrrolidin-3-yl]-6-(1H-pyrazol-4-yl)-3H-quinazolin-4-one	731247: Inhibition of ROCK1 (unknown origin)	ic50	0.0020	uM
N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]-4-(dimethylamino)benzamide	1797145: ROCK 1 Kinase Activity Assay from Article 10.1021/jm060873p: “Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity.”	ic50	0.0020	uM
N-[(2S)-1-amino-3-(3-fluorophenyl)propan-2-yl]-4-bromo-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamide	417626: Inhibition of ROCK1	ic50	0.0020	uM
N-[3-(dimethylamino)propyl]-3-[6-(1H-pyrazol-4-yl)-1,3-benzothiazol-2-yl]-3,4-dihydro-2H-chromene-6-carboxamide	468086: Inhibition of ROCK1	ic50	0.0020	uM
4-N-(2,3-dihydro-1H-inden-2-yl)-2-piperazin-1-yl-6-N-pyridin-4-ylpyrimidine-4,6-diamine	439134: Inhibition of ROCK1 by IMAP assay	ic50	0.0020	uM
N-[(3-methoxyphenyl)methyl]-1-methyl-6-(1H-pyrazol-4-yl)pyrrolo[2,3-b]pyridine-2-carboxamide	631998: Inhibition of ROCK1	ic50	0.0020	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
fasudil	decreases reaction, increases expression, decreases expression	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	increases reaction, increases expression, affects binding	2
deguelin	decreases expression	2
Y 27632	increases expression, decreases activity, decreases reaction	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Benzo(a)pyrene	increases expression, decreases expression	2
Plant Extracts	affects cotreatment, increases expression, decreases expression	2
Quercetin	increases expression	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
SHP099	decreases expression, increases reaction	1
moringin	increases expression, affects cotreatment	1
dicrotophos	decreases expression	1
oxybenzone	increases expression	1
bis(tri-n-butyltin)oxide	increases expression	1
decabromobiphenyl ether	decreases expression	1
tributyltin	increases expression	1
quercitrin	affects expression	1
cobaltous chloride	increases expression	1
scoparone	decreases expression	1
alkannin	decreases reaction, increases expression	1
tetrabromobisphenol A	decreases expression	1
bufalin	decreases expression	1
sodium bisulfide	increases activity	1
ochratoxin A	increases expression	1

ChEMBL screening assays

665 unique, capped per target: 661 binding, 3 functional, 1 admet

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
CHEMBL4481804	ADMET	Inhibition of ROCK1 (unknown origin) using STK2 as substrate measured after 4 hrs by HTRF assay	Discovery of (S)-6-methoxy-chroman-3-carboxylic acid (4-pyridin-4-yl-phenyl)-amide as potent and isoform selective ROCK2 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C7DJ	Abcam A-549 ROCK1 KO	Cancer cell line	Male
CVCL_C7E9	Abcam HCT 116 ROCK1 KO	Cancer cell line	Male
CVCL_C7EP	Abcam THP-1 ROCK1 KO	Cancer cell line	Male
CVCL_D7ZJ	Ubigene A-549 ROCK1 KO	Cancer cell line	Male
CVCL_D8UP	Ubigene HCT 116 ROCK1 KO	Cancer cell line	Male
CVCL_E0MW	Ubigene HeLa ROCK1 KO	Cancer cell line	Female
CVCL_TJ47	HAP1 ROCK1 (-) 1	Cancer cell line	Male
CVCL_TJ48	HAP1 ROCK1 (-) 2	Cancer cell line	Male
CVCL_TJ49	HAP1 ROCK1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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