JNJ-61803534

JNJ-61803534 is a potent and orally active RORγt inverse agonist with an IC50 of 9.6  nM. JNJ-61803534 has anti-inflammatory activity. JNJ-61803534 inhibits IL-17A production in human CD4+ T cells under Th17 differentiation conditions[1].

Signaling Pathways >> Metabolic Enzyme/Protease >> ROR

Research Areas >> Inflammation/Immunology

RORγt

JNJ-61803534 在转染了编码 RORγt 载体的 HEK-293 T 细胞中抑制 RORγt 转录，IC50 为 9.6 nM[1]。 JNJ-61803534 (1 nM-1 μM) 抑制人血液中分离的 CD4+ T 细胞产生 IL-17A、IL-17F IFNγ 和 IL-22[1]。 JNJ-61803534 不影响 CD4+ T 细胞的体外 Treg 分化[1]。

JNJ-61803534 (100 mg/kg，口服) 抑制小鼠血液中体外刺激产生的 IL-17A[1]。 JNJ-61803534 (3-100 mg/kg BID 或 60 mg/kg QD，p.o.) 减轻小鼠胶原诱导性关节炎 (CIA) 模型的炎症、软骨损伤和骨质破坏[1]。 JNJ-61803534 (30 和 100 mg/kg，口服) 减轻小鼠 Imiquimod (HY-B0180) 诱导的皮肤银屑病样炎症[1]。 Animal Model: Mouse collagen-induced arthritis (CIA) model[1] Dosage: 3-100 mg/kg BID or 60 mg/kg QD Administration: Oral administration (p.o.) Result: Decreased clinical arthritis scores and hind paw histopathology scores.

[1]. Xue X, et al. Preclinical and clinical characterization of the RORγt inhibitor JNJ-61803534. Sci Rep. 2021 May 26;11(1):11066.