一种衣壳组装调节剂前药提高了药物可及性，并降低了 HBsAg 和 HBeAg，可用于治疗慢性乙型肝炎。
A prodrug of the capsid assembly modulator improved druggability and lowing HBsAg and HBeAg for the treatment of chronic hepatitis B.
机构信息
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu-ChongZhi Road, Shanghai, 201203, China.
Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu-ChongZhi Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China.
出版信息
Eur J Med Chem. 2023 Sep 5;257:115485. doi: 10.1016/j.ejmech.2023.115485. Epub 2023 May 13.
CAMs were disclosed to alter cccDNA levels with sustained hepatitis B surface antigen (HBsAg) loss or seroconversion in preclinical investigation. Here, we report the discovery of a prodrug Yhhu6669 as CAMs based on the intestinal peptide transporter. This compound exhibited the promising anti-HBV activity with sustained suppression of HBV DNA, as well as HBsAg and HBeAg in the AAV HBV mouse model by oral treatment for 7 weeks and maintained for a further 8 weeks following drug withdraw. Our results show an alternative possibility for a functional cure by specific CAMs and provide the basis for the further mechanism study.
CAMs 被发现可以改变cccDNA 水平，从而在临床前研究中持续降低乙肝表面抗原 (HBsAg) 或实现血清学转换。在这里，我们报告了一种基于肠肽转运体的前药 Yhhu6669 作为 CAMs 的发现。该化合物在 AAV HBV 小鼠模型中具有持续抑制 HBV DNA、HBsAg 和 HBeAg 的有前景的抗 HBV 活性，通过口服治疗 7 周，并在停药后进一步持续 8 周。我们的结果显示了通过特定的 CAMs 实现功能性治愈的另一种可能性，并为进一步的机制研究提供了基础。
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