Document Report Card

Basic Information

ID: ALA4251585

Journal: Eur J Med Chem

Title: Accelerated skin wound healing by selective 11β-Hydroxylase (CYP11B1) inhibitors.

Authors: Emmerich J, van Koppen CJ, Burkhart JL, Engeli RT, Hu Q, Odermatt A, Hartmann RW.

Abstract: Previous studies have shown that inhibition of cortisol biosynthesis in skin leads to accelerated wound healing. Here, pyridylmethyl pyridine type 11β-hydroxylase (CYP11B1) inhibitors were optimized for topical application to avoid systemic side effects. The resulting very potent, non-toxic CYP11B1 inhibitor 14 (IC50 = 0.8 nM) exhibited good selectivity over 11β-HSD1, CYP17A1 and CYP19A1. The compound showed high stability toward human plasma (t1/2= > 150 min, as a substitute for wound fluid) and low stability toward HLS9 (t1/2 = 19 min) for rapid metabolic clearance after absorption. Compound 14 was able to accelerate wound healing in human skin.

CiteXplore: 29207342

DOI: 10.1016/j.ejmech.2017.11.018