原创力文档a renal-targeted triptolide aminoglycoside (tpag) conjugate for lowering systemic toxicities of triptolide：肾靶向的雷公藤内酯醇氨基糖苷类（tpag）共轭降低雷公藤内酯醇的全身毒性.pdfVIP
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a renal-targeted triptolide aminoglycoside (tpag) conjugate for lowering systemic toxicities of triptolide：肾靶向的雷公藤内酯醇氨基糖苷类（tpag）共轭降低雷公藤内酯醇的全身毒性
Fitoterapia 103 (2015) 242–251
Contents lists available at ScienceDirect
Fitoterapia
journal homepage: /locate/fitote
A renal-targeted triptolide aminoglycoside (TPAG) conjugate for
lowering systemic toxicities of triptolide
Bowen Qi, Xinyi Wang, Yangyang Zhou, Qiao Han, Ling He, Tao Gong, Xun Sun,
Yao Fu, Zhirong Zhang ⁎
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041 Sichuan, China
a r t i c l e i n f o a b s t r a c t
Article history: Triptolide (TP), a naturally derived compound, is proven effective in the treatment of nephritis
Received 14 February 2015 and chronic allograft nephropathy. However, the severe multiorgan toxicity greatly limited it from
Accepted in revised form 5 April 2015 further clinic use. 2-Glucosamine was demonstrated as a potential targeting ligand that could
Accepted 7 April 2015 specifically interact with megalin receptors highly expressed in renal proximal tubules. In this
Available online 11 April 2015
study, 2-glucosamine was employed as a glycosyl donor while triptolide the acceptor to afford a
nonhydrolyzable triptolide derivative-triptolide aminoglycoside (TPAG). The kidney-targeting
Keywords: efficiency, pharmacodynamic properties and safety of TPAG were thus evaluated. TPAG displayed
Glycosidic bond 6.94-fold of AUC0 − t, ki
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