555562

Rho Kinase Inhibitor XIII, RKI-1447

• Synonym(e): Rho Kinase Inhibitor XIII, RKI-1447, 1-(3-Hydroxybenzyl)-3-(4-(pyridin-4-yl)thiazol-2-yl)urea, Methanesulfonate, ROCK Inhibitor XIII, 1-(3-Hydroxybenzyl)-3-(4-(pyridin-4-yl)thiazol-2-yl)urea, Mesylate
• Empirische Formel (Hill-System): C₁₆H₁₄N₄O₂S · xCH₄O₃S
• Molekulargewicht: 326.37 (free base basis)
• UNSPSC-Code: 12352200
• NACRES: NA.77

Eigenschaften

• Assay: ≥98% (HPLC)
• Qualitätsniveau: 100
• Form: solid
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; desiccated (hygroscopic); protect from light
• Farbe: yellow-white
• Löslichkeit: DMSO: 100 mg/mL
• Versandbedingung: ambient
• Lagertemp.: −20°C

Beschreibung

Allgemeine Beschreibung

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.

Biochem./physiol. Wirkung

Cell permeable: yes

Primary Target
Rho kinases 1 & 2

Reversible: yes

Target IC₅₀: 14.5 and 6.2 nM against ROCK1 and ROCK2, respectively

Verpackung

Packaged under inert gas

Warnhinweis

Toxicity: Standard Handling (A)

Sonstige Hinweise

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

Rechtliche Hinweise

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

Sicherheitshinweise

• Lagerklassenschlüssel: 11 - Combustible Solids
• WGK: WGK 2
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable