Y-27632

Uses

Y-27632 Dihydrochloride is a salt analog of Y-27632, which is Rho-kinase inhibitor.

Definition

ChEBI: A monocarboxylic acid amide that is trans-[(1R)-1-aminoethyl]cyclohexanecarboxamide in which one of the nitrogens of the aminocarbony group is substituted by a pyridine nucleus. It has been shown to exhibit inhibitory acti ity against Rho-associated protein kinase (ROCK) enzyme.

Biological Activity

Selective inhibitor of the Rho-associated protein kinase p160ROCK. K i values are 0.14, 26, 25 and >250 μ M for p160ROCK, PKC, cAMP-dependent protein kinase and myosin light-chain kinase respectively. Also inhibits the protein kinase C-related protein kinase, PRK2 (IC 50 = 600nM). Smooth muscle relaxant and orally active in vivo . Increases survival rate of human embryonic stem (hES) cells undergoing cryopreservation.

in vivo

IC 50

ROCK-I: 220 nM (Ki); ROCK-II: 300 nM (Ki); PKN: 3.1 μM (Ki); Citron kinase: 5.3 μM (Ki); PKCα: 73 μM (Ki); PKA: 25 μM (Ki)

Background

Y-27632 is a potent and selective ATP-competitive inhibitor of Rho-associated kinases, with Ki values of 0.22 µM and 0.30 µM for ROCK1 and ROCK2, respectively. In vitro kinase assays demonstrate that Y-27632 exhibits a 20-fold greater preference for ROCK when compared to citron kinase and protein kinase N. Research studies show that Y-27632 treatment of cells leads to inhibition of ROCK phosphorylation of myosin phosphatase subunit 1 at both Thr853 and Thr696, with a much greater inhibition of Thr853 phosphorylation. Y-27632 selectively inhibits smooth-muscle contraction by inhibiting Ca2+ sensitization. Additional research indicates that Y-27632 inhibits dissociation-induced apoptosis of cultured human embryonic stem cells over numerous passages and increases cloning efficiency.

References

[1] ishizaki t1, uehata m, tamechika i, keel j, nonomura k, maekawa m, narumiya s. pharmacological properties of y-27632, a specific inhibitor of rho-associated kinases. mol pharmacol. 2000 may;57(5):976-83.