Loading…

Novel Triazolopyridine-Based BRD4 Inhibitors as Potent HIV‑1 Latency Reversing Agents

Bromodomain-containing protein 4 (BRD4) inhibitors have been proven to be a promising option for anti-HIV-1 latency therapeutics. We herein describe the design, synthesis, and anti-HIV-1 latency bioevaluation of triazolopyridine derivatives as BRD4 inhibitors. Among them, compound 13d displayed favo...

Full description

Saved in:
Bibliographic Details
Published in:ACS medicinal chemistry letters 2024-01, Vol.15 (1), p.60-68
Main Authors: Wang, Yan-Kai, Huang, Xu-Sheng, Sun, Hao, Ma, Meng-Di, Yu, Hai-Peng, Hu, Wei, Li, Zhi-Yu, Li, Zhong, Luo, Rong-Hua, Tian, Ren-Rong, Xiao, Tai-Fu, Yang, Liu-Meng, Zheng, Yong-Tang, Li, Xun
Format: Article
Language:English
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Bromodomain-containing protein 4 (BRD4) inhibitors have been proven to be a promising option for anti-HIV-1 latency therapeutics. We herein describe the design, synthesis, and anti-HIV-1 latency bioevaluation of triazolopyridine derivatives as BRD4 inhibitors. Among them, compound 13d displayed favorable HIV-1 reactivation and prominent safety profile without triggering abnormal immune activation. It exerted strong synergism when combined with the PKC activator prostratin and has the same BRD4-targeting latency mechanism as observed with JQ1, by stimulating Tat-dependent HIV-1 elongation. Besides, it neither affected the antiviral efficacies of antiviral drugs nor caused secondary infections to uninfected cells and the latency reversing potency of 13d, in turn, was not affected by different classes of antiviral drugs.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.3c00373