CYM50358 is a potent and selective sphingosine-1-phosphate receptor 4 (S1P4) antagonist, functioning by blocking the S1P₄ receptor. CYM50358 can be employed for research on immunomodulatory mechanisms[1-2].
In vitro, CYM50358 (10µM) was used to pretreat human platelets for 15 minutes, followed by stimulation with collagen (1µg/ml) for 4 minutes. CYM50358 did not significantly affect collagen-induced HSP27 phosphorylation but reversed sphingosine-1-phosphate (S1P)-induced inhibition of HSP27 phosphorylation[3]. CYM50358 (1µM) was used to pretreat murine C2C12 myoblasts for 30 minutes, followed by treatment with TGFβ1 (5ng/ml) for 18-24 hours. CYM50358 significantly attenuated TGFβ1-induced caspase-3 activation and PARP cleavage[4].
In vivo, CYM50358 (5mg/kg) was administered via intraperitoneal injection 30 minutes before OVA sensitization or 30 minutes after OVA challenge in female BALB/c mice. CYM50358 significantly inhibited the increase of eosinophils and lymphocytes in bronchoalveolar lavage fluid, reduced lung inflammation scores, suppressed mucin secretion, and lowered serum IgE and IL-4 levels[5]. CYM50358 (2.5mg/kg) was administered via intraperitoneal injection every two days starting from day 3 after rhesus rotavirus (RRV) injection until day 14 in neonatal Balb/c mice. CYM50358 significantly improved RRV-induced biliary atresia, reduced the incidence of extrahepatic biliary obstruction, alleviated liver inflammation and fibrosis, improved liver function, and increased survival rates[6].
References:
[1] Podolak I, Janeczko Z, Galanty A, et al. A triterpene saponin from Lysimachia thyrsiflora L. Acta Pol Pharm. 2007 Jan-Feb;64(1):39-43.
[2] Kitada Y, Kajita K, Taguchi K, et al. Blockade of Sphingosine 1-Phosphate Receptor 2 Signaling Attenuates High-Fat Diet-Induced Adipocyte Hypertrophy and Systemic Glucose Intolerance in Mice. Endocrinology. 2016 May;157(5):1839-51.
[3] Onuma T, Tanabe K, Kito Y, et al. Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor. Thromb Res. 2017 Aug;156:91-100.
[4] J Cencetti F, Bernacchioni C, Tonelli F, et al. TGFβ1 evokes myoblast apoptotic response via a novel signaling pathway involving S1P4 transactivation upstream of Rho-kinase-2 activation. FASEB J. 2013 Nov;27(11):4532-46.
[5] Jeon WJ, Chung KW, Lee JH, et al. Suppressive Effect of CYM50358 S1P4 Antagonist on Mast Cell Degranulation and Allergic Asthma in Mice. Biomol Ther (Seoul). 2021 Sep 1;29(5):492-497.
[6] Sun D, Wang D, Jia L, et al. S1P/S1PR4 promotes the differentiation of CD8+ tissue-resident memory T cells aggravating bile duct injury in biliary atresia. J Hepatol. 2026 Feb;84(2):385-398.
CYM50358是一种有效的、选择性的鞘氨醇-1-磷酸4（S1P4）受体拮抗剂，通过拮抗S1P4受体发挥作用。CYM50358可被用于免疫调节机制的相关研究[1-2]。
在体外，CYM50358（10μM）预处理人血小板15分钟，随后以胶原蛋白（1μg/ml）刺激4分钟，CYM50358对胶原诱导的HSP27磷酸化无显著影响，但可逆转鞘氨醇-1-磷酸（S1P）诱导的HSP27磷酸化抑制[3]。CYM50358（1μM）预处理鼠C2C12成肌细胞30分钟，随后以TGFβ1（5ng/ml）处理18-24小时。CYM50358可显著减弱TGFβ1诱导的caspase-3活化与PARP裂解[4]。
在体内，CYM50358（5mg/kg）在OVA致敏前30分钟或OVA激发后30分钟经腹腔注射，用于处理雌性BALB/c小鼠。CYM50358显著抑制了支气管肺泡灌洗液中嗜酸性粒细胞和淋巴细胞的增加、肺部炎症评分、黏蛋白分泌以及血清IgE和IL-4水平的升高[5]。CYM50358（2.5mg/kg）在rhesus rotavirus（RRV）后第3天开始，每2天一次腹腔注射，用于处理新生Balb/c小鼠直至第14天。CYM50358显著改善了RRV诱导的胆道闭锁、降低了肝外胆道阻塞发生率、减轻了肝脏炎症和纤维化、改善了肝功能并提高了生存率[6]。