Premium
Identification and characterization of novel small‐molecule inhibitors of SLC26A9
Author(s) -
Park Jinhong,
Jeon Dongkyu,
Park SoHyeon,
Namkung Wan
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02683
Subject(s) - chemistry , ic50 , pharmacology , small molecule , in vitro , biochemistry , biology
SLC26A9 (solute carrier family 26, member 9), an anion exchanger, is highly expressed epithelial cells of the respiratory tract, stomach, pancreas and kidney. SLC26A9 plays a pivotal role as an important regulator in airway inflammatory diseases and gastric acid production. In this study, a cell‐based high‐throughput screening (HTS) assay was established and performed to identify highly potent and selective small molecule inhibitors. Screening of 25,600 synthetic small molecules identified three novel SLC26A9 inhibitors, and the inhibitors were found to fully block the Cl ‐ /I ‐ exchange activity of SLC26A9 with IC 50 < 1 µM. The novel SLC26A9 inhibitors strongly inhibited both Cl ‐ /I ‐ and Cl ‐ /HCO 3 ‐ exchange activity of SLC26A9. The most potent inhibitor significantly blocked Cl ‐ /I ‐ exchange activity of SLC26A9 (IC 50 of ~100 nM) without affecting the activity of SLC26A3 (DRA), SLC26A4 (pendrin), SLC26A7, CFTR and ANO1. The novel potent and selective inhibitors of SLC26A9 are useful tool for pharmacological dissection of SLC26A9 and may be a potential therapeutic candidate for airway inflammatory diseases and hyperacidity.