An overview of small-molecule agents for the treatment of psoriasis

Abstract

Psoriasis is a prevalent, chronic inflammatory disease characterized by abnormal skin plaques. To date, physical therapy, topical therapy, systemic therapy and biologic drugs are the most commonly employed strategies for treating psoriasis. Recently, many agents have advanced to clinical trials, and some anti-psoriasis drugs have been approved, including antibody drugs and small-molecule drugs. Many antibody drugs targeting cytokines and receptors, such as interleukin (IL-17 and IL-23) and tumor necrosis factor-α (TNF-α), have been approved for the treatment of psoriasis. And numerous small-molecule agents have displayed promising activities in the treatment of psoriasis. The targets of anti-psoriasis drugs encompass phosphodiesterase IV (PDE4), Janus kinase (JAK), tyrosine kinase (TYK), retinoic acid-related orphan receptors (ROR), vitamin D receptor (VDR), Interleukin (IL), Aryl hydrocarbon receptor (AhR), Interleukin-1 receptor-associated kinase 4 (IRAK), chemoattractant-like receptor 1 (ChemR23), Sphingosine-1-phosphate receptor (S1P), A3 adenosine receptor (A3AR), Heat shock protein 90 (HSP90), The Rho-associated protein kinases (ROCK), The bromodomain and extra-terminal domain (BET), FMS-like tyrosine kinase 3 (FLT3), Tumor Necrosis Factor α Converting Enzyme (TACE), Toll-like receptors (TLR), NF-κB inducing kinase (NIK), DNA topoisomerase I (Topo I), among others. Herein, this review mainly recapitulates the advancements in the structure and enzyme activity of small-molecule anti-psoriasis agents over the last ten years, and their binding modes were also explored. Hopefully, this review will facilitate the development of novel small-molecule agents as potential anti-psoriasis drugs.

Keywords: A3AR; AhR; HSP90; IL; IRAK; JAK; PDE4; Psoriasis; ROR; Small-molecule.