METHODS OF TREATING GENERALIZED PUSTULAR PSORIASIS WITH ANTAGONIST OF CCR6 OR CXCR2

• Main Authors: YU CHAO, EBSWORTH KAREN, SINGH RAJINDER, MCMAHON JEFFREY, YANG JU, ZHANG PENGLIE, CAMPBELL JAMES J, KRASINSKI ANTONI, MALI VENKAT REDDY
• Format: Patent
• Language: Chinese; English
• Published: 30.10.2020
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

The present disclosure provides, inter alia, methods of treating generalized pustular psoriasis (GPP) by administering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C-X-C motif chemokine receptor 2 (CXCR2) antagonist. Also provided herein are methods of modulating dysregulated IL-36 signaling in a subject in need thereof and methods of reducing neutrophil, inflammatory dendritic cell (iDC), and/or CD4 T cell accumulation in a subject in need thereof, said methods, include dministering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C-X-C motif chemokine receptor 2 (CXCR2) antagonist. In some embodiments, the CCR6 and/or CXCR2 antagonist has the formula (A): 本公开尤其提供了通过施用有效量的趋化因子受体6(CCR6)拮抗剂和/或C-X-C基序趋化因子受体2(CXCR2)拮抗剂来治疗泛发性脓疱型银屑病(GPP)的方法。本文还提供了在有需要的受试者中调节失调的IL-36信号传导的方法和在有需要的受试者中减少嗜中性白细胞、炎性树突细胞(iDC)和/或CD4T细胞聚积的方法，所述方法包括施用有效量的趋化因子受体6(CCR6)拮抗剂和/或CXC基序趋化因子受体2(CXCR2)拮抗剂。在一些实施方式中，CCR6和/或CXCR2拮抗剂具有下式：