Rho Kinase Inhibitor XIII, RKI-1447-Calbiochem

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一般描述

A cell-permeable pyridylthiazolyl-urea that acts as a potent, ATP site-targeting, Rho Kinase inhibitor (IC₅₀= 14.5 and 6.2 nM against ROCK1 and ROCK2, respectively), displaying much reduced potency against PKA, PKN1/PRK1, p70S6K/RPS6kB1, AKT1, MRCKa/CDC42BPA (85.5%, 80.5%, 61.9%, 56.0%, and 50.4% inhibition, respectively, at 1 ?M) and little or no activity against 15 other kinases (IC₅₀>1 ?M). Selectively inhibits ROCK-dependent MLC-2 Ser19 and MYPT-1 Thr696 phosphorylations (effective conc. 0.1 to 1 ?M in MDA-MB-231, MDA-MB-468, and H1299 cultures), but not mTORC2-dependent Akt Ser473, PAK-dependent Mek Ser298, or S6K-dependent S6 Ser240/244 phosphorylations (up to 10 ?M in MDA-MB-231 cells). Shown to inhibit MDA-MB-231 invasion (by 53% and 85%, respectively, with 1 and 10 ?M inhibitor) and anchorage-independent colony formation (IC₅₀= 709 nM)in vitroand be efficacious in suppressing established tumor expansion in a murine ErbB2 mammary cancer model (8.8% vs. 68.3% average tumor size expansion in 14 days, respectively, with or without treatment; 14 dailly i.p. doses at 200 mg/kg)in vivo.
A cell-permeable pyridylthiazolyl-urea that acts as a potent, ATP site-targeting, Rho Kinase inhibitor (IC₅₀= 14.5 and 6.2 nM against ROCK1 and ROCK2, respectively), displaying much reduced potency against PKA, PKN1/PRK1, p70S6K/RPS6kB1, AKT1, MRCKa/CDC42BPA (85.5%, 80.5%, 61.9%, 56.0%, and 50.4% inhibition, respectively, by 1 ?M RKI-1447) or 15 other kinases. Selectively inhibits ROCK-dependent, but not mTORC2-dependent, cellular phosphorylations (effective conc. 0.1 to 1 ?M in MDA-MB-231, MDA-MB-468, and H1299 cultures). Shown to be efficacious in suppressing established tumor expansion in a murine ErbB2 mammary cancer model (200 mg/kg/day i.p.)in vivo.

包装

10 mg in Glass bottle
Packaged under inert gas

生化/生理作用

Cell permeable: yes
Reversible: yes
Primary Target
Rho kinases 1 & 2
Target IC₅₀: 14.5 and 6.2 nM against ROCK1 and ROCK2, respectively

警告

Toxicity: Standard Handling (A)

其他说明

Patel, R.A., et al. 2012.Cancer Res.72,5025.

法律信息

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

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