2. Academic Validation
  3. Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review

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

  • Dermatol Ther (Heidelb). 2023 Dec;13(12):3031-3042. doi: 10.1007/s13555-023-01054-3.
Andrew Blauvelt 1,  Richard G Langley 2,  Kenneth B Gordon 3,  Jonathan I Silverberg 4,  Kilian Eyerich 5 6,  Morten O A Sommer 7 8,  Jakob Felding 7,  Richard B Warren 9
Affiliations

Affiliations

  • 1 Oregon Medical Research Center, 9495 SW Locust Street, Suite G, Portland, OR, 97223, USA. [email protected].
  • 2 Division of Clinical Dermatology and Cutaneous Science, Department of Medicine, Dalhousie University and Nova Scotia Health, Halifax, Canada.
  • 3 Froedtert Hospital and the Medical College of Wisconsin, Milwaukee, WI, USA.
  • 4 George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
  • 5 Technical University of Munich, Munich, Germany.
  • 6 Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
  • 7 UNION Therapeutics A/S, Hellerup, Denmark.
  • 8 Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark (DTU), Lyngby, Denmark.
  • 9 Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, Manchester, UK.
PMID: 37924462 DOI: 10.1007/s13555-023-01054-3
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.

Keywords

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

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