Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review

Authors

Andrew Blauvelt, Oregon Medical Research Center, 9495 SW Locust Street, Suite G, Portland, OR, 97223, USA. ablauvelt@oregonmedicalresearch.com.
Richard G. Langley, Division of Clinical Dermatology and Cutaneous Science, Department of Medicine, Dalhousie University and Nova Scotia Health, Halifax, Canada.
Kenneth B. Gordon, Froedtert Hospital and the Medical College of Wisconsin, Milwaukee, WI, USA.
Jonathan I. Silverberg, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Kilian Eyerich, Technical University of Munich, Munich, Germany.
Morten O. Sommer, UNION Therapeutics A/S, Hellerup, Denmark.
Jakob Felding, UNION Therapeutics A/S, Hellerup, Denmark.
Richard B. Warren, Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, Manchester, UK.

Document Type

Journal Article

Publication Date

12-1-2023

Journal

Dermatology and therapy

Volume

13

Issue

12

DOI

10.1007/s13555-023-01054-3

Keywords

Nerandomilast; Orismilast; PDE4 inhibitors; PDE4B; PDE4D; PF-07038124; Zatolmilast

Abstract

For decades, topical corticosteroids have been the mainstay of treatment for mild-to-moderate inflammatory skin diseases, even though only short-term use is approved for these agents and systemic inflammation is not addressed. Increased understanding of the immunopathogenesis of these conditions, especially for psoriasis and atopic dermatitis, has facilitated the development of antibody-based drugs that neutralize single key cytokines or their associated receptors, such as interleukin (IL)-17A/F, IL-23, and IL-17RA in psoriasis and IL-13 and IL-4Rα in atopic dermatitis. However, oral therapy is still preferred by many patients owing to the ease of use and needle-free administration. Phosphodiesterase 4 (PDE4) inhibitors have been approved for both oral and topical use for inflammatory skin diseases. In this review, we present a summary of an emerging class of selective PDE4B/D inhibitors under clinical development and compare the differences in selectivity of this new generation of PDE4 inhibitors with the less selective currently approved PDE4 inhibitors.

APA Citation

Blauvelt, Andrew; Langley, Richard G.; Gordon, Kenneth B.; Silverberg, Jonathan I.; Eyerich, Kilian; Sommer, Morten O.; Felding, Jakob; and Warren, Richard B., "Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review" (2023). GW Authored Works. Paper 4056.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4056

Department

Dermatology