Medicinal Chemistry Research

, Volume 27, Issue 2, pp 583–591 | Cite as

Enzymic synthesis and biological evaluation of injectable glutathione-everolimus

  • Haibo Wang
  • Xiaohe Zheng
  • Lifei Mao
  • Liang Qin
  • Tianmin Zhu
Original Research

Abstract

An enzymic synthesis of glutathione-everolimus is reported. This process has been optimized and scaled up with high reproducibility and yields, which will facilitate the development of such conjugate. The stability of the conjugate supported that this prodrug can be prepared into lyophilized solid, which is to be reconstituted with 0.9% sodium chloride for injection before intravenous infusion. And the results of species-related drug release experiment displayed that the performance of the conjugate in human plasma, rat and monkey was similar. Moreover, the in vivo efficacy of glutathione-everolimus in the treatment of renal cell carcinoma was investigated in detail. The conjugate was proved to be an effective, safe and well-tolerated injectable prodrug in the treatment of renal cell carcinoma. The results indicated that three times injection with a high dosage in 1 week can achieve much better in vivo efficacy, and no obvious toxic response was observed.

Keywords

Everolimus Glutathione Renal cell carcinoma Prodrug Drug delivery mTOR 

Notes

Acknowledgements

This work was financially supported by the Key Science and Technology Innovation Team of Zhejiang Province (2013TD10).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_2084_MOESM1_ESM.pdf (1 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Zhejiang Hongyuan pharmaceutical Co., Ltd.LinhaiChina
  2. 2.Zhejiang Hisun pharmaceutical Co., Ltd.TaizhouChina

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