ROCK inhibitor

• CAT Number: I005216
• CAS Number: 867017-68-3
• Molecular Formula: C18H13ClF2N6O
• Molecular Weight: 402.80
• Purity: ≥95%
• Synonyms: 6-chloro-4-N-[3,5-difluoro-4-[(3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]phenyl]pyrimidine-2,4-diamine
• Target: TGF-beta/Smad
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 0.6 nM(ROCK1); 1.1 nM (ROCK2) [1]
• InChI: InChI=1S/C18H13ClF2N6O/c1-8-7-24-17-15(8)12(2-3-23-17)28-16-10(20)4-9(5-11(16)21)25-14-6-13(19)26-18(22)27-14/h2-7H,1H3,(H,23,24)(H3,22,25,26,27)
• InChIKey: NRSGWEVTVGZDFC-UHFFFAOYSA-N
• SMILES: CC1=CNC2=NC=CC(=C12)OC3=C(C=C(C=C3F)NC4=CC(=NC(=N4)N)Cl)F

ROCK inhibitors（Cat No.:I005216）are compounds that target Rho-associated protein kinases (ROCK), enzymes involved in regulating cell shape, motility, and contraction. These kinases play a critical role in processes like smooth muscle contraction, cell migration, and tissue remodeling. By inhibiting ROCK activity, these drugs can affect a variety of physiological processes, including reducing vascular tone, promoting wound healing, and potentially modulating fibrosis. ROCK inhibitors are being explored in the treatment of diseases such as glaucoma, cardiovascular disorders, and fibrosis-related conditions. They may also have applications in neurodegenerative diseases by protecting neurons from damage.

Reference

[1]. Kast, R.; Schirok, H.; Figueroa-Perez, S.; Mittendorf, J.; Gnoth, M. J.; Cardiovascular effects of a novel potent and highly selective azaindole-based inhibitor of Rho-kinase. British Journal of Pharmacology (2007), 152(7), 1070-1080.
Abstract
BACKGROUND AND PURPOSE: Rho-kinase (ROCK) has been implicated in the pathophysiology of altered vasoregulation leading to hypertension. Here we describe the pharmacological characterization of a potent, highly selective and orally active ROCK inhibitor, the derivative of a class of azaindoles, azaindole 1 (6-chloro-N4-{3,5-difluoro-4-[(3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-phenyl}pyrimidine-2,4-diamine). EXPERIMENTAL APPROACH: Pharmacological characterization of azaindole 1 was performed with human recombinant ROCK in vitro. Vasodilator activity was determined using isolated vessels in vitro and different animal models in vivo. KEY RESULTS: This compound inhibited the ROCK-1 and ROCK-2 isoenzymes with IC50 s of 0.6 and 1.1 nM in an ATP-competitive manner. Although ATP-competitive, azaindole 1 was inactive against 89 kinases (IC50>10 microM) and showed only weak activity against an additional 21 different kinases (IC50=1-10 microM). Only the kinases TRK und FLT3 were inhibited by azaindole 1 in the sub-micromolar range, albeit with IC50 values of 252 and 303 nM, respectively. In vivo, azaindole 1 lowered blood pressure dose-dependently after i.v. administration in anaesthetized normotensive rats. In conscious normotensive and spontaneously hypertensive rats azaindole 1 induced a dose-dependent decrease in blood pressure after oral administration without inducing a significant reflex increase in heart rate. In anaesthetized dogs, azaindole 1 induced vasodilatation with a moderately elevated heart rate. CONCLUSIONS AND IMPLICATIONS: Azaindole 1 is representative of a new class of selective and potent ROCK inhibitors and is a valuable tool for the elucidation of the role of ROCK in the cardiovascular system.