UK 383367

UK 383367 is a novel procollagen C-protein (PCP) inhibitor being investigated for the treatment of post-surgical dermal scarring, which potently inhibits the activity of PCP with the value of 50% inhibition concentration IC₅₀ of 44 nM, as well as a selective inhibitor of matrix metalloproteinases (MMPs) with values of IC₅₀ >60,000 nM for MMP-2 and >10,000 nM for MMP-1, MMP-3, MMP-9 and MMP-4. Although the mechanism is not clear yet, UK 383367 also exhibits weak inhibitory effects against phosphodiesterase-4 (PDE-4) enzyme, including PDE-4a, PDE-4b, PDE-4c and PDE-4d, with values of IC₅₀ of 1.8 μM, 1.5 μM, 2.4 μM and 0.9 μM respectively.

Reference

G. A. Allan, J. I. Gedge, A. N. R. Nedderman, S. J. Roffey, H. F. Small and R. Webster. Pharmacokinetics and metabolism of UK-383,367 in rats and dogs: a rationale for long-lived plasma radioactivity. Xenobiotica 2006; 36(5): 399-418

Bailey S, Fish PV, Billotte S, Bordner J, Greiling D, James K, McElroy A, Mills JE, Reed C, Webster R.ff. Succinyl hydroxamates as potent and selective non-peptidic inhibitors of procollagen C-proteinase: design, synthesis, and evaluation as topically applied, dermal anti-scarring agents. Bioorg Med Chem Lett. 2008;18(24):6562-6567