GSK429286A

SKU: orb1305239

Description

GSK429286A is a potent and selective ROCK1/2 inhibitor with IC50 values of 14 nM and 63 nM, respectively. It is widely used in research to investigate Rho/ROCK signaling pathways in cellular processes such as cytoskeletal regulation, and has been applied in both in vitro and in vivo models of neurological and cardiovascular function.

Research Area

Cell Biology, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 864082-47-3
• MW: 432.37
• Purity: 97.68% (May vary between batches)
• Formula: C₂₁H₁₆F₄N₄O₂
• SMILES: CC1=C(C(CC(=O)N1)c1ccc(cc1)C(F)(F)F)C(=O)Nc1cc2cn[nH]c2cc1F
• Target: ROCK
• Solubility: Ethanol:4 mg/mL (9.25 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.63 mM);DMSO:140 mg/mL (323.8 mM)

Bioactivity

• Target IC50:
  ROCK2:63 nM|p70 S6K:1940 nM|ROCK1:14 nM|RSK:780 nM
• In Vivo:
  GSK429286A at a concentration of 1 μM significantly reduces the activity of ROCK2 by 20-fold, whereas it only reduces MSK1 activity by approximately 5-fold at the same concentration. This compound exhibits higher selectivity as an ROCK2 inhibitor compared to the commonly used inhibitor Y-27632, showing negligible inhibition against LRRK2 even at 30 μM, with an IC50 that is 500 times higher for ROCK2. Similar to GSK269962A, GSK429286A at 10 μM can eliminate phosphorylation at Thr850 of MYPT induced either by the baseline or by the G14V-Rho mutant in HEK-293 cells, demonstrating effects similar to those of H-1152 and Y-27632 and consistent with ROCK-mediated phosphorylation. Regardless of the presence of G14V-Rho, GSK429286A does not affect the phosphorylation of ERM proteins. Additionally, GSK429286A mildly inhibits RSK (IC50: 0.78 μM) and p70S6K (IC50: 1.94 μM). It also significantly inhibits the dilation of rat aortic rings (IC50: 190 nM).
• In Vitro:
  GSK429286A (3-30 mg/kg, p.o.) significantly reduces the mean arterial pressure in spontaneous hypertensive rats in a dose-dependent manner, with a maximum reduction of 50 mmHg approximately 2 hours after administering a dose of 30 mg/kg. In male Sprague-Dawley rats, the oral bioavailability of GSK429286A is 61%.

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, inhibit, GSK429286A, GSK-429286A, ROCK, ROK, ROCK1, ROCK2, Rho-kinase, RHO 15, RHO15, RHO-15, Rho-associated kinase, Rho-associated protein kinase

Compound Identifiers

PubChem CID

11373846