9PGV

HIV Capsid Hexamer bound to Compound 24

これはPDB形式変換不可エントリーです。

9PGV の概要

• エントリーDOI: 10.2210/pdb9pgv/pdb
• 分子名称: HIV-1 capsid, N-methyl-N-phenyl-3-(pyridin-3-yl)-N~2~-{[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetyl}-L-alaninamide (3 entities in total)
• 機能のキーワード: capsid, p24, hiv-1, viral protein
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 312935.64

構造登録者

Somoza, J.R.,Anderson, R.L.,Villasenor, A.G.,Ferrao, R.D. (登録日: 2025-07-08, 公開日: 2025-10-08, 最終更新日: 2025-10-29)

主引用文献

Canales, E.,Tse, W.,Schroeder, S.D.,Chou, C.H.,Liu, Q.,Zhang, J.,Lazerwith, S.E.,Morganelli, P.,Saito, R.D.,Brizgys, G.,Li, J.,Wu, Q.,Graupe, M.,Halcomb, R.L.,Desai, M.,Cannizzaro, C.,Hu, E.,Perry, J.K.,Villasenor, A.G.,Somoza, J.R.,Ferrao, R.D.,Swaminathan, S.,Zheng, J.,Lu, B.,Mwangi, J.,Wang, K.,Subramanian, R.,Smith, B.J.,Rhodes, G.,Rowe, W.,Sauer, D.,Lad, L.,Papalia, G.A.,Clancy, S.,Stepan, G.J.,Yu, H.,Sakowicz, R.,Shi, B.,Carr, G.,Bam, R.A.,Tsai, L.K.,Singer, E.,Hansen, D.,Mulato, A.,Yant, S.R.,Cihlar, T.,Link, J.O.
Discovery of Lenacapavir: First-in-Class Twice-Yearly Capsid Inhibitor for HIV-1 Treatment and Pre-exposure Prophylaxis.
J.Med.Chem., 68:21072-21094, 2025

PubMed Abstract: The HIV capsid is essential to the virus lifecycle, making it a promising target for therapeutic intervention. In 2006, a screening campaign was initiated to identify small molecules capable of disrupting the protein-protein interactions required for self-assembly of the 1500 capsid monomers that form the 37 MDa fullerene cone-shaped capsid. Numerous compound design cycles over many years were undertaken to discover the complex structural elements that together afford the multistage HIV capsid inhibitor lenacapavir. Lenacapavir is the most potent (HIV-1 EC = 105 pM) and longest-acting HIV antiviral to date, with a unique twice-yearly dosing regimen. Clinically, lenacapavir has demonstrated robust efficacy for both HIV-1 treatment and prevention, and, remarkably, achieved 100% protection in women for the first time. These findings represent a significant advancement in treatment and prevention of HIV-1 infection, offering the potential to profoundly impact the global course of the HIV epidemic.

PubMed: 41032707
DOI: 10.1021/acs.jmedchem.5c01625

実験手法

X-RAY DIFFRACTION (2.3 Å)