8I71

Hepatitis B virus core protein Y132A mutant in complex with Linvencorvir (RG7907), a Hepatitis B Virus (HBV) Core Protein Allosteric Modulator (CpAM)

8I71 の概要

• エントリーDOI: 10.2210/pdb8i71/pdb
• 分子名称: Capsid protein, CHLORIDE ION, ISOPROPYL ALCOHOL, ... (7 entities in total)
• 機能のキーワード: capsid assembly inhibitor, antiviral protein, viral protein
• 由来する生物種: Hepatitis B virus subtype adyw
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 109678.26

構造登録者

Zhou, Z.,Xu, Z.H. (登録日: 2023-01-30, 公開日: 2023-03-22, 最終更新日: 2024-10-23)

主引用文献

Zhang, W.,Guo, L.,Liu, H.,Wu, G.,Shi, H.,Zhou, M.,Zhang, Z.,Kou, B.,Hu, T.,Zhou, Z.,Xu, Z.,Zhou, X.,Zhou, Y.,Tian, X.,Yang, G.,Young, J.A.T.,Qiu, H.,Ottaviani, G.,Xie, J.,Mayweg, A.V.,Shen, H.C.,Zhu, W.
Discovery of Linvencorvir (RG7907), a Hepatitis B Virus Core Protein Allosteric Modulator, for the Treatment of Chronic HBV Infection.
J.Med.Chem., 66:4253-4270, 2023

PubMed Abstract: Described herein is the first-time disclosure of Linvencorvir (RG7907), a clinical compound and a hepatitis B virus (HBV) core protein allosteric modulator, for the treatment of chronic HBV infection. Built upon the core structure of hetero aryl dihydropyrimidine, RG7907 was rationally designed by combining all the drug-like features of low CYP3A4 induction, potent anti-HBV activity, high metabolic stability, low hERG liability, and favorable animal pharmacokinetic (PK) profiles. In particular, the chemistry strategy to mitigate CYP3A4 induction through introducing a large, rigid, and polar substituent at the position that has less interaction with the therapeutic biological target (HBV core proteins herein) is of general interest to the medicinal chemistry community. RG7907 demonstrated favorable animal PK, pharmacodynamics, and safety profiles with sufficient safety margins supporting its clinical development in healthy volunteers and HBV-infected patients.

PubMed: 36896968
DOI: 10.1021/acs.jmedchem.3c00173

実験手法

X-RAY DIFFRACTION (1.6 Å)