Structure-optimized dihydropyranoindole derivative GIBH-LRA002 potentially reactivated viral latency in primary CD4+ T lymphocytes of chronic HIV-1 patients

Qing Yang; Yuyang Ding; Fengling Feng; Enxiang Pan; Xiaozhen Fan; Xiuchang Ma; Ling Chen; Junling Zhao; Caijun Sun

doi:10.1039/c7md00327g

Structure-optimized dihydropyranoindole derivative GIBH-LRA002 potentially reactivated viral latency in primary CD4+ T lymphocytes of chronic HIV-1 patients

Medchemcomm. 2017 Jul 25;8(9):1806-1809. doi: 10.1039/c7md00327g. eCollection 2017 Sep 1.

Authors

Qing Yang^{1

2}, Yuyang Ding^{1

3}, Fengling Feng^{1

4}, Enxiang Pan^{1

3}, Xiaozhen Fan^{1

4}, Xiuchang Ma¹, Ling Chen^{1

2}, Junling Zhao⁵, Caijun Sun¹

Affiliations

¹ Guangzhou Institutes of Biomedicine and Health (GIBH) , Chinese Academy of Sciences , Guangzhou 510530 , China . Email: Sun_caijun@gibh.ac.cn.
² State Key Laboratory of Respiratory Disease , The First Affiliated Hospital of Guangzhou Medical University , Guangzhou , 510120 , China.
³ University of Chinese Academy of Sciences , Beijing , 100049 , China.
⁴ School of Life Sciences , University of Science and Technology of China (USTC) , Hefei , 230027 , China.
⁵ Institute of Medicinal Chemistry , School of Pharmaceutical Sciences , Sun Yat-sen University , Guangzhou 510006 , P.R. China . Email: zhaojunl@iccas.ac.cn.

Abstract

Based on structure modification and a high-throughput Jurkat-Lat cell screening model, we found that GIBH-LRA002, ethyl-2-amino-3-cyano-9-methyl-4-(trifluoromethyl)-4,9-dihydropyrano[2,3-b]indole-4-carboxylate, effectively reactivated the latent proviruses in a Jurkat-Lat cell line and primary CD4+ T cells from both chronic SIV-infected rhesus macaques and HIV-1 patients but without inducing systemic activation, making this compound attractive for potentially treating HIV-1 infection.