7S76

HBV CAPSID Y132A WITH COMPOUND 10b AT 2.5A RESOLUTION

7S76 の概要

• エントリーDOI: 10.2210/pdb7s76/pdb
• 分子名称: Capsid protein, (1-methyl-1H-1,2,4-triazol-3-yl)methyl {(4S)-1-[(3-chloro-4-fluorophenyl)carbamoyl]-2-methyl-2,4,5,6-tetrahydrocyclopenta[c]pyrrol-4-yl}carbamate (2 entities in total)
• 機能のキーワード: core, viral protein, inhibitor, viral protein-inhibitor complex, viral protein/inhibitor
• 由来する生物種: Hepatitis B virus genotype A (HBV)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 110708.65

構造登録者

Olland, A.M.,Suto, R.K. (登録日: 2021-09-15, 公開日: 2022-05-04, 最終更新日: 2024-11-13)

主引用文献

Cole, A.G.,Kultgen, S.G.,Mani, N.,Ardzinski, A.,Fan, K.Y.,Thi, E.P.,Dorsey, B.D.,Stever, K.,Chiu, T.,Tang, S.,Daly, O.,Phelps, J.R.,Harasym, T.,Olland, A.,Suto, R.K.,Sofia, M.J.
The identification of highly efficacious functionalised tetrahydrocyclopenta[ c ]pyrroles as inhibitors of HBV viral replication through modulation of HBV capsid assembly.
Rsc Med Chem, 13:343-349, 2022

PubMed Abstract: Disruption of the HBV viral life cycle with small molecules that prevent the encapsidation of pregenomic RNA and viral polymerase through binding to HBV core protein is a clinically validated approach to inhibiting HBV viral replication. Herein we report the further optimisation of clinical candidate AB-506 through core modification with a focus on increasing oral exposure and oral half-life. Maintenance of high levels of anti-HBV cellular potency in conjunction with improvements in pharmacokinetic properties led to multi-log reductions in serum HBV DNA following low, once-daily oral dosing for key analogues in a preclinical animal model of HBV replication.

PubMed: 35434625
DOI: 10.1039/d1md00318f

実験手法

X-RAY DIFFRACTION (2.5 Å)