Journal
DRUG DISCOVERY TODAY
Volume 24, Issue 12, Pages 2234-2246Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2019.08.007
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Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [22568]
- Universita degli Studi del Piemonte Orientale [393]
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) [2017WJZ9W9]
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A soft drug (SD) displays a metabolically labile spot and, after having exerted its activity in the site of action, undergoes a fast metabolism, leading to inactive metabolites. The SD approach has recently found widespread application in the dermatological field because it provides a means of localising the therapeutic effect in skin, while minimising systemic exposure. The literature is rapidly growing of successful examples of compounds targeting sphingosine-l-phosphate receptor 1 (S1PR1), transient receptor potential vanilloid 1 (TRPV1), Janus kinase (JAK), caspase 1, and histone deacetylase (HDAC), for the treatment of skin inflammatory, autoimmune, and oncological diseases. As a demonstration of the potential of this strategy, the SD approach recently led to the approval of crisaborole, a soft phosphodiesterase 4 (PDE4) inhibitor, for atopic dermatitis, while other agents are in clinical development.
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