| Literature DB >> 29207342 |
Juliette Emmerich1, Chris J van Koppen2, Jens L Burkhart2, Roger T Engeli3, Qingzhong Hu1, Alex Odermatt3, Rolf W Hartmann4.
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.Entities:
Keywords: 11β-hydroxylase (CYP11B1) inhibitors; 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1); Chronic wounds; Topical application; Wound healing
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Year: 2017 PMID： 29207342 DOI： 10.1016/j.ejmech.2017.11.018
Source DB: PubMed Journal: Eur J Med Chem ISSN： 0223-5234 Impact factor: 6.514