Synthesis and evaluation of an injectable everolimus prodrug.
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.
Zhejiang Hisun Pharmaceutical Co., Ltd., 46 Waisha Rd., Taizhou, Zhejiang 318000, PR China. Electronic address: whb@hisunpharm.com.
Haibo
H
Wang
Zhejiang Hisun Pharmaceutical Co., Ltd., 46 Waisha Rd., Taizhou, Zhejiang 318000, PR China.
Xiaohe
X
Zheng
Zhejiang Hisun Pharmaceutical Co., Ltd., 46 Waisha Rd., Taizhou, Zhejiang 318000, PR China.
Zhengjiang
Z
Cai
Zhejiang Hisun Pharmaceutical Co., Ltd., 46 Waisha Rd., Taizhou, Zhejiang 318000, PR China.
Ou
O
Yu
Zhejiang Hisun Pharmaceutical Co., Ltd., 46 Waisha Rd., Taizhou, Zhejiang 318000, PR China.
Shan
S
Zheng
Zhejiang Hisun Pharmaceutical Co., Ltd., 46 Waisha Rd., Taizhou, Zhejiang 318000, PR China. Electronic address: zhut@hisunpharm.com.
Tianmin
T
Zhu
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D045744:Cell Line, Tumor; D000068338:Everolimus / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D012995:Solubility
D000970:Antineoplastic Agents; D011355:Prodrugs; D000068338:Everolimus
Everolimus; Glutathione; Injectable; Long-acting; Prodrug; mTOR