MLS000532223 is a high affinity, selective inhibitor of Rho family GTPases, with EC50 ranging from 16 μM to 120 μM. Small GTPases are key regulators of cellular activity .
Rho GTPases comprise a family of molecular switches that control signal transduction pathways in eukaryotic cells. A conformational change induced upon binding GTP promotes an interaction with target (effector) proteins to generate a cellular response{{Alan Hall. Rho family GTPases. Biochem Soc Trans
. 2012 Dec 1;40(6):1378-82. |https://pubmed.ncbi.nlm.nih.gov/23176484/}}.Rho-associated kinase (Rho-kinase/ROCK/ROK) is an effector of the small GTPase Rho and belongs to the AGC family of kinases. Rho-kinase has pleiotropic functions including the regulation of cellular contraction, motility, morphology, polarity, cell division, and gene expression[2].Rho/ROCK signal pathway induces cytoskeletal reorganization, cell migration and stress fiber formation, affects endothelial permeability, tissue constriction and growth, involves in diabetic nephropathy, eye disease, cancer, heart disease, nerve injury disease, hypertension, radiation injury and leukemia[3]. The expression of Rho-kinase itself is mediated by the protein kinase C/NF-kappaB pathway with an inhibitory and stimulatory modulation by estrogen and nicotine, respectively. At the cellular level, Rho-kinase mediates VSMC contraction, stimulates VSMC proliferation and migration, and enhances inflammatory cell motility[4].MLS000532223 is a high affinity, selective inhibitor of Rho family GTPases, with EC50 values ranging from 16 μM to 120 μM. MLS000532223 prevents GTP binding to several GTPases. It prevents GTP binding to several GTPases in a dose-dependent manner,and modulates Rho-family GTP-binding kinetics.MLS000532223 is active in cell-based assays and inhibits EGF-stimulated Rac 1 activation.MLS000532223 inhibits actin rearrangements and changes in cell morphology that are downstream of Rho family GTPase activation.MLS000532223 (10 μM) modulates actin remodeling in mast cells.MLS000532223 (10 μM) inhibits ligand-stimulated β-hexosaminidase secretion of RBL cells[5].
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