Soft drugs for dermatological applications: recent trends. Issue 12 (December 2019)

• Record Type: Journal Article
• Authors: Aprile, Silvio; Serafini, Marta; Pirali, Tracey
• Is Part Of: Drug discovery today. Volume 24:Issue 12(2019)
• Page Start: 2234
• Page End: 2246
• Publication Date: 2019-12
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2019.08.007
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: A dermatological SD is stable in skin and is rapidly inactivated once entering systemic circulation. The SD design allows the development of safer drugs. The design and development of a successful SD should fulfil a set of softness criteria. Soft targeting has recently involved PDE4, S1PR1, TRPV1, JAK, caspase 1 and HDAC. Abstract : 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-1-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. Teaser: The soft drug approach is an effective strategy to define the action of topical dermatological drugs in the skin and obtain safer drugs.