Recommended Tool Compounds for Modifying the Cystic Fibrosis Transmembrane Conductance Regulator Channel Variants

被引:1
作者
Han, Xiaoxuan [1 ]
Li, Danni [1 ]
Zhu, Yimin [1 ]
Schneider-Futschik, Elena K. [1 ]
机构
[1] Univ Melbourne, Sch Biomed Sci, Fac Med Dent & Hlth Sci, Dept Biochem & Pharmacol, Parkville, Vic 3010, Australia
基金
英国医学研究理事会;
关键词
cystic fibrosis; CFTR modulators; drug accumulation; Elexacaftor/Tezacaftor/Ivacaftor; SMALL-MOLECULE CORRECTORS; CFTR CHLORIDE CHANNEL; WILD-TYPE; TEZACAFTOR-IVACAFTOR; CHEMICAL CORRECTOR; IN-VITRO; GENISTEIN; MECHANISM; DELTA-F508; RESCUE;
D O I
10.1021/acsptsci.3c00362
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Cystic fibrosis (CF) is a genetic disorder arising from variations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to multiple organ system defects. CFTR tool compounds are molecules that can modify the activity of the CFTR channel. Especially, patients that are currently not able to benefit from approved CFTR modulators, such as patients with rare CFTR variants, benefit from further research in discovering novel tools to modulate CFTR. This Review explores the development and classification of CFTR tool compounds, including CFTR blockers (CFTRinh-172, GlyH-101), potentiators (VRT-532, Genistein), correctors (VRT-325, Corr-4a), and other approved and unapproved modulators, with detailed descriptions and discussions for each compound. The challenges and future directions in targeting rare variants and optimizing drug delivery, and the potential synergistic effects in combination therapies are outlined. CFTR modulation holds promise not only for CF treatment but also for generating CF models that contribute to CF research and potentially treating other diseases such as secretory diarrhea. Therefore, continued research on CFTR tool compounds is critical.
引用
收藏
页码:933 / 950
页数:18
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