Smith S R, Terminelli C, Epps S, Watnick A, Umland S
Department of Allergy and Inflammation, Schering Corporation, Bloomfield, NJ 07003.
Immunopharmacol Immunotoxicol. 1987;9(2-3):333-59. doi: 10.3109/08923978709035218.
Sch 24937 (6-bromo-5-chloro-2-1[(methylsulfonyl) acetyl] 3-(2-pyridyl indole) was previously shown to be an immunosuppressant with potent inhibitory effects on B lymphocyte mediated immune responses. The present investigation was primarily designed to compare the immunopharmacological profile of Sch 24937 with that of cyclosporin A (CSA) a well-known immunosuppressive drug that has selective effects on T-lymphocyte-mediated immune responses. The results show that while the immunosuppressive activity of CSA in vitro is superior to that of Sch 24937, in general the latter agent is a more potent inhibitor of immune responses in vivo. The activity of Sch 24937 in rat models of adjuvant arthritis and experimental allergic encephalomyelitis is also described. While Sch 24937 exhibits the type of immunopharmacological profile that is likely to yield a good therapeutic effect in the treatment of immune-mediated chronic inflammatory diseases, hepatotoxicity associated with the compound precludes its development for the treatment of non-life threatening human autoimmune conditions.
Sch 24937（6-溴-5-氯-2-1[(甲基磺酰基)乙酰基]3-(2-吡啶基吲哚)）先前已被证明是一种免疫抑制剂，对B淋巴细胞介导的免疫反应具有强大的抑制作用。本研究主要旨在比较Sch 24937与环孢素A（CSA）的免疫药理学特征，环孢素A是一种著名的免疫抑制药物，对T淋巴细胞介导的免疫反应具有选择性作用。结果表明，虽然CSA在体外的免疫抑制活性优于Sch 24937，但总体而言，后者在体内是一种更有效的免疫反应抑制剂。还描述了Sch 24937在佐剂性关节炎和实验性变应性脑脊髓炎大鼠模型中的活性。虽然Sch 24937表现出在免疫介导的慢性炎症性疾病治疗中可能产生良好治疗效果的免疫药理学特征类型，但与该化合物相关的肝毒性排除了其用于治疗非危及生命的人类自身免疫性疾病的开发。
