A novel water-soluble everolimus prodrug, glutathione-everolimus, was designed and synthesized by introducing an endogenous tripeptide with an acetyl as the linker. The improvement in water solubility allowed the conjugate to be developed into an injectable drug. The results of biological evaluation in vitro and in vivo suggested that the prodrug was more effective and long acting than everolimus. Meanwhile, the pharmacokinetics study in vivo confirmed that the delivery of everolimus through the injection of the prodrug can overcome the low bioavailability of oral everolimus.

中文翻译：

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注射用依维莫司前药的合成与评价

通过引入以乙酰基为连接基的内源三肽，设计并合成了新型水溶性依维莫司前药谷胱甘肽-依维莫司。水溶性的改善使缀合物发展为可注射药物。体外和体内生物学评估的结果表明，前药比依维莫司更有效，作用时间更长。同时，体内药代动力学研究证实，通过注射前药来递送依维莫司可以克服口服依维莫司的低生物利用度。