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ID: ALA4387717

Journal: Bioorg Med Chem Lett

Title: Structure guided drug design to develop kallikrein 5 inhibitors to treat Netherton syndrome.

Authors: Walker AL, Bingham RP, Edgar EV, Ferrie A, Holmes DS, Liddle J, Polyakova O, Rella M, Smith KJ, Thorpe JH, Wang Y, White GV, Young RJ, Hovnanian A.

Abstract: The connection between Netherton syndrome and overactivation of epidermal/dermal proteases particularly KLK5 has been well established. To treat sufferers of this severe condition we wished to develop a topical KLK5 inhibitor in order to normalise epidermal shedding and reduce the associated inflammation and itching. In this paper we describe structure-based optimisation of a series of brightly coloured weak KLK5 inhibitors into colourless, non-irritant molecules with good KLK5 activity and selectivity over a range of serine proteases.

CiteXplore: 31005442

DOI: 10.1016/j.bmcl.2019.04.022