Advance in development of HepDirect prodrugs, liver targeting nucleoside reverse transcriptase inhibitors
ZHU Chuan-bao
ZHONG Bo-hua
Abstract：The drugs targeting specific organs, tissues or cells can enhance drug efficacy and reduce ad-verse effects. Targeting can be achieved by carriers such as antibodies, peptides, natural and synthetic polymers, and carbohydrate- or peptide-labeled nanoparticles and liposomes. However, there are lots of disadvantages in above means. Drug exposure to extravascular sites often limits drug-conjugate exchange across the endothelial barrier. Advances of drug conjugates remain slow, which is due to higher manufacturing costs, conjugate-induced immunogenic reactions, and limitations in drug loading and the route of administration. Erion et al discovered a novel class of phosphate and phosphonate prodrugs, which were named HepDirect prodrugs. The HepDirect prodrugs are oxidized specifically by the P450 isoenzyme family CYP3A4, and release the active phosphates and phosphonates. In both animal and clinical studies, liver-targeting have been observed and have no side effect-related toxicities. This review is focused on the principles, stability, by-product and representative drugs of HepDirect prodrugs.
Keywords：nucleoside analoguesHepDirect prodrugliver-targeting
Publication Date：2010-01-01
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：6( 284-289 )