5U6E

Crystal structure of clade A/E HIV-1 gp120 core in complex with NBD-14010

5U6E の概要

• エントリーDOI: 10.2210/pdb5u6e/pdb
• 分子名称: clade A/E 93TH057 HIV-1 gp120 core, 2-acetamido-2-deoxy-beta-D-glucopyranose, N-{(1S)-2-amino-1-[5-(hydroxymethyl)-4-methyl-1,3-thiazol-2-yl]ethyl}-5-(4-chloro-3-fluorophenyl)-1H-pyrrole-2-carboxamide, ... (5 entities in total)
• 機能のキーワード: hiv-1, nbd-14010, virus entry antagonist, small molecule, viral protein
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83596.84

構造登録者

Kwon, Y.D.,Debnath, A.K.,Kwong, P.D. (登録日: 2016-12-07, 公開日: 2017-03-22, 最終更新日: 2024-10-30)

主引用文献

Curreli, F.,Kwon, Y.D.,Belov, D.S.,Ramesh, R.R.,Kurkin, A.V.,Altieri, A.,Kwong, P.D.,Debnath, A.K.
Synthesis, Antiviral Potency, in Vitro ADMET, and X-ray Structure of Potent CD4 Mimics as Entry Inhibitors That Target the Phe43 Cavity of HIV-1 gp120.
J. Med. Chem., 60:3124-3153, 2017

PubMed Abstract: In our attempt to optimize the lead HIV-1 entry antagonist, NBD-11021, we present in this study the rational design and synthesis of 60 new analogues and determination of their antiviral activity in a single-cycle and a multicycle infection assay to derive a comprehensive structure-activity relationship (SAR). Two of these compounds, NBD-14088 and NBD-14107, showed significant improvement in antiviral activity compared to the lead entry antagonist in a single-cycle assay against a large panel of Env-pseudotyped viruses. The X-ray structure of a similar compound, NBD-14010, confirmed the binding mode of the newly designed compounds. The in vitro ADMET profiles of these compounds are comparable to that of the most potent attachment inhibitor BMS-626529, a prodrug of which is currently undergoing phase III clinical trials. The systematic study presented here is expected to pave the way for improving the potency, toxicity, and ADMET profile of this series of compounds with the potential to be moved to the early preclinical development.

PubMed: 28266845
DOI: 10.1021/acs.jmedchem.7b00179

実験手法

X-RAY DIFFRACTION (2.095 Å)