4NYF

HIV integrase in complex with inhibitor

4NYF の概要

• エントリーDOI: 10.2210/pdb4nyf/pdb
• 分子名称: Integrase, (2S)-tert-butoxy[4-(4-chlorophenyl)-2-methylquinolin-3-yl]ethanoic acid, CADMIUM ION, ... (4 entities in total)
• 機能のキーワード: allosteric inhibitor, ncini, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Human immunodeficiency virus type 1
• 細胞内の位置: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P0C6F2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37178.85

構造登録者

Coulombe, R.,Fader, L. (登録日: 2013-12-10, 公開日: 2014-06-25, 最終更新日: 2023-09-20)

主引用文献

Fader, L.D.,Malenfant, E.,Parisien, M.,Carson, R.,Bilodeau, F.,Landry, S.,Pesant, M.,Brochu, C.,Morin, S.,Chabot, C.,Halmos, T.,Bousquet, Y.,Bailey, M.D.,Kawai, S.H.,Coulombe, R.,LaPlante, S.,Jakalian, A.,Bhardwaj, P.K.,Wernic, D.,Schroeder, P.,Amad, M.,Edwards, P.,Garneau, M.,Duan, J.,Cordingley, M.,Bethell, R.,Mason, S.W.,Bos, M.,Bonneau, P.,Poupart, M.A.,Faucher, A.M.,Simoneau, B.,Fenwick, C.,Yoakim, C.,Tsantrizos, Y.
Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1.
ACS Med Chem Lett, 5:422-427, 2014

PubMed Abstract: An assay recapitulating the 3' processing activity of HIV-1 integrase (IN) was used to screen the Boehringer Ingelheim compound collection. Hit-to-lead and lead optimization beginning with compound 1 established the importance of the C3 and C4 substituent to antiviral potency against viruses with different aa124/aa125 variants of IN. The importance of the C7 position on the serum shifted potency was established. Introduction of a quinoline substituent at the C4 position provided a balance of potency and metabolic stability. Combination of these findings ultimately led to the discovery of compound 26 (BI 224436), the first NCINI to advance into a phase Ia clinical trial.

PubMed: 24900852
DOI: 10.1021/ml500002n

実験手法

X-RAY DIFFRACTION (1.9 Å)