ROCK1
ROCK1 is a RhoA effector serine/threonine kinase that regulates actomyosin cytoskeleton organization, smooth-muscle contraction, cell migration, and cell-shape control[1][2]. Mechanistically, ROCK1 promotes myosin light-chain phosphorylation and actomyosin contractility, and caspase-3 cleavage converts ROCK1 into an active apoptotic effector that drives membrane blebbing[3]. In vivo, ROCK1-deficient mice show failed eyelid and ventral body-wall closure, supporting its role in epithelial morphogenesis and actomyosin bundle assembly[4]. ROCK1 also regulates Beclin1-mediated autophagy, linking ROCK1 signaling to the balance between apoptosis and autophagy[8]. Compared with ROCK2, ROCK1 shows isoform-specific biology: ROCK1 destabilizes stress fibers through MLC2 phosphorylation and peripheral actomyosin contraction, whereas ROCK2 stabilizes actin through cofilin phosphorylation[5]. In glioblastoma models, ROCK1 is upregulated relative to normal brain tissue, and ROCK1 knockdown reduces proliferation and alters substrate-dependent migration, while ROCK2 knockdown produces different migration and proliferation effects[6]. For experimental applications, ROCK inhibitors provide tools to test ROCK-dependent contraction, motility, invasion, glaucoma, asthma, cancer, and cardiovascular mechanisms, although many compounds inhibit both ROCK1 and ROCK2[7].
References:
- [1]. Julian L, et al. Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions. Small GTPases. 2014;5:e29846. [Content Brief]
- [2]. Riento K, et al. Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol. 2003 Jun;4(6):446-56. [Content Brief]
- [3]. Sebbagh M, et al. Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol. 2001 Apr;3(4):346-52. [Content Brief]
- [4]. Shimizu Y, et al. ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles. J Cell Biol. 2005 Mar 14;168(6):941-53. [Content Brief]
- [5]. Shi J, et al. Distinct roles for ROCK1 and ROCK2 in the regulation of cell detachment. Cell Death Dis. 2013 Feb 7;4(2):e483. [Content Brief]
- [6]. Mertsch S, et al. Opposing signaling of ROCK1 and ROCK2 determines the switching of substrate specificity and the mode of migration of glioblastoma cells. Mol Neurobiol. 2014 Apr;49(2):900-15. [Content Brief]
- [7]. Feng Y, et al. Rho Kinase (ROCK) Inhibitors and Their Therapeutic Potential. J Med Chem. 2016 Mar 24;59(6):2269-300. [Content Brief]
- [8]. Gurkar AU, et al. Identification of ROCK1 kinase as a critical regulator of Beclin1-mediated autophagy during metabolic stress. Nat Commun. 2013;4:2189. [Content Brief]
All Product Categories
-
ROCK1 Related Products (60)
Related Products (60)
-
Antibodies (1)
-
GSK180736A
0 ImagesGSK180736A is potent Rho-associated coiled-coil kinase 1 (ROCK1) inhibitor with an IC50 of 100 nM. GSK180736A is also a selective and ATP-competitive G protein-coupled receptor kinase 2 (GRK2) inhibitor with an IC50 of 0.77 μM.
-
Verosudil
0 ImagesSynonyms: AR-12286Verosudil (AR-12286) is a ROCK inhibitor. Verosudil has equal inhibitory activity against ROCK1 and ROCK2 (Ki: 2 nM). Verosudil is less selective for PKA, PKCT, MRCKA, and CAM2A (Ki: 69 nM, 9322 nM, 28 nM, 5855 nM, respectively). Verosudil increases trabecular outflow capacity to reduce intraocular pressure. Verosudil is useful in the study of glaucoma and ocular hypertension.
-
NRL-1049
0 ImagesSynonyms: BA-1049 free baseNRL-1049 (BA-1049 (free base)) is an orally available and selective ROCK2 inhibitor with IC50 values of 0.59 µM for ROCK2 and 26 µM for ROCK1, respectively. NRL-1049 modulates ROCK signaling, preserves blood-brain barrier integrity, reduces edema, seizures and hemorrhage, and alleviates cerebral cavernous malformation lesion burden. NRL-1049 can be used for the study of acute brain injury, ischemic stroke, and cerebral cavernous malformations.
-
GSK-25
0 ImagesGSK-25 is a potent, selective and orally bioavailable ROCK1 inhibitor (IC50=7 nM). GSK-25 maintains good selectivity against a panel of 31 kinases (>100 fold), as well as RSK1 and p70S6K (RSK1: IC50=398 nM, p70S6K: IC50=1 μM). GSK-25 inhibits P450 profile (IC50s of 2.5, 5.2, 2.5 µM for CYP2C9, CYP2D6, CYP3A4, respectively).
-
Sovesudil hydrochloride
0 ImagesSynonyms: PHP-201 hydrochloride; AMA0076 hydrochlorideSovesudil (PHP-201) hydrochloride is a potent, ATP-competitive, locally acting Rho kinase (ROCK) inhibitor with IC50s of 3.7 and 2.3 nM for ROCK-I and ROCK-II, respectively. Sovesudil hydrochloride lowers intraocular pressure (IOP) without inducing hyperemia.
-
ROCK1-IN-1
0 ImagesROCK1-IN-1 is a potent selective ROCK1 inhibitor with a Ki of 540 nM. ROCK1-IN-1 can be used for the research of hypertension.
-
LIMK-IN-1
0 ImagesLIMK-IN-1 (Compound 14) is an inhibitor of LIM-Kinase (LIMK), with IC50s of 0.5 nM and 0.9 nM for LIMK1 and LIMK2, respectively. LIMK-IN-1 can be used for ocular hypertension and associated glaucoma research.
-
DJ4
0 ImagesDJ4 is a ATP-competitive inhibitor of ROCK1/2 (IC50 values:5 and 50 nM) and MRCKα/β (IC50 values:10 and 100 nM). DJ4 blocks stress fiber formation and inhibits migration and invasion of cancer cells. DJ4 can be used for study of lung cancer, breast cancer, and pancreatic (PANC-1) cancer.
