Biologics: Targets & Therapy (Jun 2025)
IRAK4 Targeting: A Breakthrough Approach to Combat Hidradenitis Suppurativa
Abstract
Hui Zhang,1,* Zhi Liu,1,* Bozhao Qin,2 Dapeng Cheng,1 Peisheng Chen,1 Xinling Bi1 1Department of Dermatology, The First Affiliated Hospital of Naval Medical University, Shanghai, People’s Republic of China; 2Unit for Drug and Instrument Supervision and Inspection of Wuxi Joint Logistics Support Center, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinling Bi, Department of Dermatology, The First Affiliated Hospital of Naval Medical University, Shanghai, People’s Republic of China, Email [email protected]: Hidradenitis suppurativa (HS), a chronic inflammatory condition, features recurrent, painful lesions in the perineal area, severely impairing patients’ quality of life. Despite its clinical significance, HS pathogenesis remains incompletely understood, and effective treatments are scarce. Interleukin-1 receptor-associated kinase 4 (IRAK4) is located downstream of IL-1R/TLR in the IL-1R/TLR signaling pathway, which is upstream of the end products of the pathway. IRAK4-targeted drugs can potentially block this pathway, reducing cytokine secretion and alleviating HS symptoms. This paper comprehensively reviews IRAK4 and its family members’ physiological functions, systematically examines the IRAK family’s roles in the IL-1R/TLR pathway, with a focus on IRAK4, analyzes IRAK4’s specific role in HS, strengthening the theoretical basis for using IRAK4-targeted drugs. The text also covers representative drugs of the major biologics currently used in the treatment of HS and describes the IRAK4 inhibitor Zimlovisertib and the IRAK4 degrader KT-474, along with a discussion of the current status of drugs that inhibit IRAK4 in the treatment of HS and the challenges they face.Keywords: Hidradenitis suppurativa, interleukin-1 receptor-associated kinase 4, IL-1R/TLR signalling pathway, cytokines
