9NLP

HIV-1 Reverse Transcriptase with New Non-Nucleoside Reverse Transcriptase Inhibitor 12126065

これはPDB形式変換不可エントリーです。

9NLP の概要

• エントリーDOI: 10.2210/pdb9nlp/pdb
• EMDBエントリー: 49521
• 分子名称: Reverse transcriptase p66 subunit, Reverse transcriptase p51 subunit, 4-({5-amino-1-[6-(2-cyanoethyl)naphthalene-1-sulfonyl]-1H-1,2,4-triazol-3-yl}amino)-2-chlorobenzonitrile (3 entities in total)
• 機能のキーワード: reverse transcriptase, viral protein
• 由来する生物種: HIV-1 06TG.HT008; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 117827.66

構造登録者

Young, M.A.,Lane, T.R.,Raman, R.,Nelson, J.A.E.,Riabova, O.,Kazakova, E.,Monakhova, N.,Tsedilin, A.,Rees, S.D.,Quinnell, D.,Chang, G.,Ekins, S. (登録日: 2025-03-03, 公開日: 2025-05-07, 最終更新日: 2025-05-21)

主引用文献

Young, M.A.,Lane, T.R.,Raman, R.,Nelson, J.A.E.,Riabova, O.,Kazakova, E.,Monakhova, N.,Tsedilin, A.,Rees, S.D.,Quinnell, D.,Makarov, V.,Chang, G.,Ekins, S.
Cryo-EM Structure of HIV-1 Reverse Transcriptase with N -Phenyl-1-(phenylsulfonyl)-1 H -1,2,4-triazol-3-amine: A New HIV-1 Non-nucleoside Inhibitor.
Acs Infect Dis., 11:1257-1267, 2025

PubMed Abstract: The use of highly active antiretroviral therapy (HAART) has made the human immunodeficiency virus (HIV) a chronic disease rather than a terminal disease. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are an important component of HAART, although we are seeing clinically relevant drug-resistant mutants such that there is a need to develop new molecules. We recently identified a new class of -phenyl-1-(phenylsulfonyl)-1-1,2,4-triazol-3-amine HIV-1 NNRTI, with one known as compound 12126065, with sub nanomolar (nM) potency in TZM-bl cells (HeLa cells expressing CD4, CCR5, and CXCR4) with no in vivo acute or subacute toxicity. We now describe the cryo-EM structure of this molecule (resolution of 3.53 Å) and compare it to analogues and other known NNRTIs. We also describe the synthesis and activity of five additional analogues of this class of compounds, some of which have promising activity against a K103N/Y181C (A17) double mutant, which will enable the design of future molecules.

PubMed: 40304150
DOI: 10.1021/acsinfecdis.5c00189

実験手法

ELECTRON MICROSCOPY (3.53 Å)