Sphingosine-1-Phosphate Receptor Subtype 1 (S1P1) Modulator IMMH001 Regulates Adjuvant- and Collagen-Induced Arthritis

Jing Jin; Ming Ji; Rong Fu; Mingjin Wang; Nina Xue; Qiong Xiao; Jingpin Hu; Xiaojian Wang; Fangfang Lai; Dali Yin; Xiaoguang Chen

doi:10.3389/fphar.2019.01085

Sphingosine-1-Phosphate Receptor Subtype 1 (S1P1) Modulator IMMH001 Regulates Adjuvant- and Collagen-Induced Arthritis

Front Pharmacol. 2019 Sep 19:10:1085. doi: 10.3389/fphar.2019.01085. eCollection 2019.

Authors

Jing Jin¹, Ming Ji¹, Rong Fu¹, Mingjin Wang¹, Nina Xue¹, Qiong Xiao¹, Jingpin Hu², Xiaojian Wang¹, Fangfang Lai¹, Dali Yin¹, Xiaoguang Chen^{1

2}

Affiliations

¹ State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Sphingosine-1-phosphate receptor subtype 1 (S1P₁) is essential for lymphocyte egress from lymphoid organs into systemic circulation and provides a well-defined drug target for autoimmune disorders. IMMH001, also called SYL930, is a specific S1P₁/S1P₄/S1P₅ modulator. Here, we investigated the potential therapeutic effect of IMMH001 on rheumatoid arthritis (RA). IMMH001 rendered periphery blood lymphocytes insensitive to the egress signal from secondary lymphoid organs. Importantly, in both rat adjuvant-induced arthritis and collagen-induced arthritis models, IMMH001 treatment significantly inhibited the progression of RA and RA-associated histological changes in the joints of Sprague-Dawley rats, including hind paw swelling and arthritic index, and thus reduced the pathological score. Furthermore, IMMH001 markedly decreased proinflammatory cytokine and chemokine release from the damaged joints. These data demonstrated that IMMH001 is a promising drug candidate for RA treatment.

Keywords: S1P1; S1P1 modulator; animal model; lymphocyte homing; rheumatoid arthritis.