Rigosertib is a styryl benzyl sulfone that inhibits growth of tumor cells and acts as a RAS mimetic by binding to Ras binding domains of RAS effectors. A recent study attributed rigosertib’s mechanism of action to microtubule binding. In that study, rigosertib was obtained from a commercial vendor. We compared the purity of clinical-grade and commercially sourced rigosertib and found that commercially sourced rigosertib contains approximately 5% ON01500, a potent inhibitor of tubulin polymerization. Clinical-grade rigosertib, which is free of this impurity, does not exhibit tubulin-binding activity. Cell lines expressing mutant β-tubulin have also been reported to be resistant to rigosertib. However, our study showed that these cells failed to proliferate in the presence of rigosertib at concentrations that are lethal to wild-type cells. Rigosertib induced a senescence-like phenotype in the small percentage of surviving cells, which could be incorrectly scored as resistant using short-term cultures.

Rigosertib 是一种苯乙烯基苄基砜，可抑制肿瘤细胞的生长，并通过与 RAS 效应子的 Ras 结合域结合而充当 RAS 模拟物。最近的一项研究将 rigosertib 的作用机制归因于微管结合。在该研究中，rigosertib 是从一家商业供应商处获得的。我们比较了临床级和商业来源的 rigosertib 的纯度，发现商业来源的 rigosertib 含有大约 5% 的 ON01500，一种有效的微管蛋白聚合抑制剂。不含这种杂质的临床级 rigosertib 不表现出微管蛋白结合活性。据报道，表达突变 β-微管蛋白的细胞系对 rigosertib 具有耐药性。然而，我们的研究表明，这些细胞在 rigosertib 存在且浓度对野生型细胞致命的情况下无法增殖。