小分子，包括 Janus 激酶 (JAK) 抑制剂和 1-磷酸鞘氨醇受体调节剂 (S1PRM)，是治疗炎症性肠病 (IBD) 的有前景的新疗法。小分子比生物制剂表现出更可预测的药代动力学，不太可能诱导免疫反应，并且可以口服给药。 JAK 抑制剂通过阻断 JAK 酶的活性发挥作用，从而阻止随后的信号转导子和转录激活子 (STAT) 蛋白的磷酸化和激活。托法替尼和菲戈替尼被批准用于治疗溃疡性结肠炎（UC），而乌帕替尼被批准用于治疗溃疡性结肠炎和克罗恩病。然而，JAK 抑制剂会增加带状疱疹、癌症、主要不良心血管事件和静脉血栓栓塞的风险。 S1PRM 与淋巴细胞上的 S1PR，特别是 S1PR1 结合。这种相互作用抑制淋巴细胞离开淋巴结并迁移到肠道，从而减少肠粘膜的炎症和免疫反应。 Ozanimod 和 etrasimod 是被批准用于治疗 UC 的 S1PRM，但它们可能引起心动过缓、传导障碍和黄斑水肿等副作用。总体而言，JAK 抑制剂和 S1PRM 在治疗 IBD 方面具有显着的益处，尽管它们的潜在副作用需要仔细监测。

Small molecules, including Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor modulators (S1PRMs), are promising new treatments for inflammatory bowel disease (IBD). Small molecules exhibit more predictable pharmacokinetics than biologics, are less likely to induce immune responses, and can be administered orally. JAK inhibitors function by blocking the activity of JAK enzymes, which prevents the subsequent phosphorylation and activation of signal transducer and activator of transcription (STAT) proteins. Tofacitinib and filgotinib are approved for treating ulcerative colitis (UC), while upadacitinib is approved for UC and Crohn's disease. Nevertheless, JAK inhibitors can increase the risk of herpes zoster, cancer, major adverse cardiovascular events, and venous thromboembolism. S1PRMs bind to S1PRs, particularly S1PR1, on lymphocytes. This interaction inhibits lymphocytes from exiting the lymph nodes and migrating to the gut, thereby reducing inflammation and the immune response in the intestinal mucosa. Ozanimod and etrasimod are S1PRMs approved for the treatment of UC, but they can cause side effects such as bradycardia, conduction disorder, and macular edema. Overall, JAK inhibitors and S1PRMs offer significant benefits in managing IBD, although their potential side effects require careful monitoring.