9N3H

Crystal structure of HBV capsid with compound 18

This is a non-PDB format compatible entry.

Summary for 9N3H

• Entry DOI: 10.2210/pdb9n3h/pdb
• Descriptor: Capsid protein, N-[3-(difluoromethyl)phenyl]-5-[{[(1s,4s)-4-hydroxycyclohexyl]amino}(oxo)acetyl]-1,2,4-trimethyl-1H-pyrrole-3-carboxamide (3 entities in total)
• Functional Keywords: hbv capsid, viral protein
• Biological source: Hepatitis B virus genotype D subtype adw (isolate United Kingdom/adyw/1979) (HBV-D)
• Total number of polymer chains: 2
• Total formula weight: 36904.11

Authors

White, A.,Lakshminarasimhan, D.,Cakici, O.,Suto, R. (deposition date: 2025-01-31, release date: 2025-07-02, Last modification date: 2025-07-30)

Primary citation

Liu, B.,Yao, J.,Haimowitz, T.,Benetatos, C.A.,Boyd, S.A.,Condon, S.M.,Burns, C.J.,White, A.,Lakshminarasimhan, D.,Suto, R.K.,Cakici, O.,Drager, A.S.,Hart, S.G.E.,Pevear, D.C.,Coburn, G.A.
Discovery of VNRX-9945, a Potent, Broadly Active Capsid Assembly Modulator as a Clinical Candidate for the Treatment of Chronic Hepatitis B Virus Infection.
Acs Med.Chem.Lett., 16:1209-1216, 2025

PubMed Abstract: Targeting the capsid protein of the hepatitis B virus (HBV) has emerged as a promising strategy for developing new antiviral therapies. In this study, we report the discovery of a novel series of pyrrole oxo-carboxamide compounds as HBV capsid assembly modulators (CAMs) that block viral replication. Through a process of focused structure-activity relationship (SAR) optimization, we identified compound (VNRX-9945), which exhibited excellent and broad antiviral activity against multiple HBV genotypes in vitro, along with favorable pharmacokinetic profiles across multiple species. Additionally, demonstrated robust efficacy in the adeno-associated virus mouse model of HBV (AAV-HBV) infection. This compound has advanced into Phase 1 clinical trials to evaluate its safety and pharmacokinetics in healthy volunteers, to enable treatment of chronic HBV infections.

PubMed: 40666476
DOI: 10.1021/acsmedchemlett.5c00315

Experimental method

X-RAY DIFFRACTION (2.543 Å)