8I71

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

Summary for 8I71

• Entry DOI: 10.2210/pdb8i71/pdb
• Descriptor: Capsid protein, CHLORIDE ION, ISOPROPYL ALCOHOL, ... (7 entities in total)
• Functional Keywords: capsid assembly inhibitor, antiviral protein, viral protein
• Biological source: Hepatitis B virus subtype adyw
• Total number of polymer chains: 6
• Total formula weight: 109678.26

Authors

Zhou, Z.,Xu, Z.H. (deposition date: 2023-01-30, release date: 2023-03-22, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.6 Å)