8GBU

Hepatitis B capsid Y132A mutant with compound AB-506

Summary for 8GBU

• Entry DOI: 10.2210/pdb8gbu/pdb
• Descriptor: Capsid protein, (1-methyl-1H-1,2,4-triazol-3-yl)methyl {(1S)-4-[(3-chloro-4-fluorophenyl)carbamoyl]-7-fluoro-2,3-dihydro-1H-inden-1-yl}carbamate, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: hepatitis b, y132a, capsid, viral protein
• Biological source: Hepatitis B virus
• Total number of polymer chains: 6
• Total formula weight: 116610.70

Authors

Horanyi, P.S.,Mayclin, S.J. (deposition date: 2023-02-28, release date: 2023-09-06, Last modification date: 2024-10-09)

Primary citation

Cole, A.G.,Kultgen, S.G.,Mani, N.,Quintero, J.G.,Yi Fan, K.,Ardzinski, A.,Stever, K.,Dorsey, B.D.,Phelps, J.R.,Lee, A.C.H.,Thi, E.P.,Chiu, T.,Tang, S.,Horanyi, P.S.,Mayclin, S.J.,Harasym, T.O.,Sofia, M.J.
Design, synthesis, and structure-activity relationship of a bicyclic HBV capsid assembly modulator chemotype leading to the identification of clinical candidate AB-506.
Bioorg.Med.Chem.Lett., 94:129456-129456, 2023

PubMed Abstract: Disruption of the HBV capsid assembly process through small-molecule interaction with HBV core protein is a validated target for the suppression of hepatitis B viral replication and the development of new antivirals. Through combination of key structural features associated with two distinct series of capsid assembly modulators, a novel aminochroman-based chemotype was identified. Optimization of anti-HBV potency through generation of SAR in addition to further core modifications provided a series of related functionalized aminoindanes. Key compounds demonstrated excellent cellular potency in addition to favorable ADME and pharmacokinetic profiles and were shown to be highly efficacious in a mouse model of HBV replication. Aminoindane derivative AB-506 was subsequently advanced into clinical development.

PubMed: 37633618
DOI: 10.1016/j.bmcl.2023.129456

Experimental method

X-RAY DIFFRACTION (2.5 Å)