Rho Kinase Inhibitor XIII, RKI-1447-Calbiochem

C₁₆H₁₄N₄O₂S · xCH₄O₃S

326.37 (free base basis)

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 µM) and little or no activity against 15 other kinases (IC₅₀ >1 µM). Selectively inhibits ROCK-dependent MLC-2 Ser19 and MYPT-1 Thr696 phosphorylations (effective conc. 0.1 to 1 µM 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 µM in MDA-MB-231 cells). Shown to inhibit MDA-MB-231 invasion (by 53% and 85%, respectively, with 1 and 10 µM inhibitor) and anchorage-independent colony formation (IC₅₀ = 709 nM) in vitro and 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 µM RKI-1447) or 15 other kinases. Selectively inhibits ROCK-dependent, but not mTORC2-dependent, cellular phosphorylations (effective conc. 0.1 to 1 µM 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.

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

Toxicity: Standard Handling (A)

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

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

100

≥98% (HPLC)

solid

Calbiochem^®

OK to freeze
desiccated (hygroscopic)
protect from light

yellow-white

DMSO: 100 mg/mL

ambient

−20℃

10 mg in Glass bottle
Packaged under inert gas

11 - Combustible Solids

WGK 2