SMS2-IN-1 is a potent and highly selective inhibitor of sphingomyelin synthase 2 (SMS2), with an IC50 value of 6.5nM for SMS2 and 1000nM for SMS1. SMS2-IN-1 binds to wild-type SMS2 with a Kd of 37nM, with S227 and H229 identified as key residues for binding[1].
In vitro, pre-treatment with 30µM SMS2-IN-1 for 30min blocked TcdB3-induced migracytosis in NRK cells overexpressing Tspan4-mCherry[2]. Treatment with 25µM SMS2-IN-1 for 16h significantly inhibited the formation of migrasome-like structures in NRK cells stably expressing Tspan4-GFP[3].
References:
[1] Adachi R, et al. Discovery and characterization of selective human sphingomyelin synthase 2 inhibitors. Eur J Med Chem. 2017 Aug 18;136:283-293.
[2] Li D, Yang Q, Luo J, Xu Y, Li J, Tao L. Bacterial toxins induce non-canonical migracytosis to aggravate acute inflammation. Cell Discov. 2024;10(1):112.
[3] Wang D, Wang H, Wan W, et al. Engineered migrasomes provide a robust and thermally stable vaccination platform. Elife. 2025;13:RP97621.
SMS2-IN-1是一种强效且高选择性的鞘磷脂合成酶2（SMS2）抑制剂，对SMS2的IC50值为6.5nM，对SMS1的IC50值为1000nM。SMS2-IN-1与野生型SMS2的Kd值为37nM，其中S227和H229被确定为结合的关键残基[1]。
体外实验中，30µM SMS2-IN-1预处理30分钟可阻断TcdB3在Tspan4-mCherry过表达的NRK细胞中诱导的胞吐迁移体的产生[2]。在稳定表达Tspan4-GFP的NRK细胞中，以25µM SMS2-IN-1处理16小时，可显著抑制类迁移体结构的形成[3]。