Structure guided drug design to develop kallikrein 5 inhibitors to treat Netherton syndrome
| Autor: | Gemma Victoria White, Duncan S. Holmes, Monika Rella, James H. Thorpe, Robert J. Young, Ann Louise Walker, Kathrine J. Smith, Emma V. Edgar, Alain Hovnanian, Oxana Polyakova, Ryan P. Bingham, Yichen Wang, Alan R. Ferrie, John Liddle |
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| Rok vydání: | 2019 |
| Předmět: |
Drug
Proteases media_common.quotation_subject Clinical Biochemistry Pharmaceutical Science Inflammation Pharmacology 01 natural sciences Biochemistry Drug Discovery medicine Humans Netherton syndrome Molecular Biology media_common integumentary system 010405 organic chemistry Chemistry Organic Chemistry KLK5 Kallikrein medicine.disease 0104 chemical sciences 010404 medicinal & biomolecular chemistry LEKTI Netherton Syndrome Drug Design Molecular Medicine Itching Kallikreins medicine.symptom |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 29:1454-1458 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2019.04.022 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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