Discovery and Characterization of Zelnecirnon (RPT193), a Potent and Selective CCR4 Antagonist for Allergic Disorders

Journal of Medicinal Chemistry 2026

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Authors: Mikhail Zibinsky, Delia Bradford, Dirk G. Brockstedt, Ross Corriden, Jeffrey J. Jackson, Scott Jacobson, Sherry Jiao, Paul D. Kassner, John M. Ketcham, Lisa A. Marshall, Akinori Okano, Omar Robles
+8 more Jacob B. Schwarz, Oezcan Talay, Parcharee Tivitmahaisoon, Dianna Lester-Zeiner, Heather Milestone, Damian L. Trujillo, Ashkaan Younai, David J. Wustrow
DOI: 10.1021/acs.jmedchem.5c01678
Cited by: 1
References: 34

Abstract

cells, in particular T helper type 2 (Th2) immune cells, allowing these cells to migrate to the inflamed tissue and exacerbate the disease by the production of proinflammatory cytokines such as IL-4, IL-5, and IL-13. Antagonism of the CCR4 receptor is an attractive way to restrict this migration, which offers potential disease modification. Herein we report the discovery of Zelnecirnon (RPT193), a potent and selective small-molecule CCR4 antagonist. Zelnecirnon can effectively inhibit CCR4-induced chemotaxis, has attractive DMPK and drug-like properties, and can reduce CCR4 receptor surface expression. In an in vivo model of atopic dermatitis, Zelnecirnon demonstrated efficacy similar to those of approved biologics in this indication, thus demonstrating the proof of concept for this mechanism and its potential as an effective oral alternative.

Fields of Study & Subjects

Dermatology and Skin Diseases Asthma and respiratory diseases Chemokine receptors and signaling

Publication details

Journal / source
Journal of Medicinal Chemistry
Publisher
American Chemical Society (ACS)
Volume
69
Issue
3
Pages
1982–1998
Publication date
23 January 2026
Language
EN