555562

Rho Kinase Inhibitor XIII, RKI-1447

• 别名: 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
• 经验公式（希尔记法）: C₁₆H₁₄N₄O₂S · xCH₄O₃S
• 分子量: 326.37 (free base basis)
• 分類程式碼代碼: 12352200
• NACRES: NA.77

属性

• 化驗: ≥98% (HPLC)
• 品質等級: 100
• 形狀: solid
• 製造商／商標名: Calbiochem^®
• 儲存條件: OK to freeze; desiccated (hygroscopic); protect from light
• 顏色: yellow-white
• 溶解度: DMSO: 100 mg/mL
• 運輸包裝: ambient
• 儲存溫度: −20°C

说明

一般說明

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.

生化／生理作用

Cell permeable: yes

Primary Target
Rho kinases 1 & 2

Reversible: yes

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

包裝

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

其他說明

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

法律資訊

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

安全信息

• 儲存類別代碼: 11 - Combustible Solids
• 水污染物質分類（WGK）: WGK 2
• 閃點（°F）: Not applicable
• 閃點（°C）: Not applicable