ARTICLE | Distillery Therapeutics


October 20, 2016 7:00 AM UTC

In vitro, rat and pig studies identified a phenoxyaminoindane-based SLC9A3 inhibitor that could help treat sleep apnea. Screening of a small molecule library in a cell-based assay, followed by chemical synthesis and in vitro testing to optimize a series of phenoxyaminoindane hits, yielded a compound (SAR197) that inhibited mouse, cat, pig and rat SLC9A3 with IC50 values of 10-78 nM. In a pig model of sleep apnea, intraduodenal delivery of the compound decreased upper airway collapsibility compared with vehicle. In rats and pigs, the compound had oral bioavailability of 42% and 18-98%, and half-lives of 2.7 and 8.1-33 hours, respectively. Next steps by Sanofi could include testing the compound’s activity against human SCL9A3...