CDER167, a dual inhibitor of URAT1 and GLUT9, is a novel and potent uricosuric candidate for the treatment of hyperuricemia.

ABSTRACT: Urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) are important targets for the development of uric acid-lowering drugs. We previously showed that the flexible linkers of URAT1 inhibitors could enhance their potency. In this study we designed and synthesized CDER167, a novel RDEA3710 analogue, by introducing a linker (methylene) between the naphthalene and pyridine rings to increase flexibility, and characterized its pharmacological and pharmacokinetics properties in vitro and in vivo. We showed that CDER167 exerted dual-target inhibitory effects on both URAT1 and GLUT9: CDER167 concentration-dependently inhibited the uptake of [¹⁴C]-uric acid in URAT1-expressing HEK293 cells with an IC₅₀ value of 2.08 ± 0.31 μM, which was similar to that of RDEA3170 (its

SUBMITTER: Zhao ZA 

PROVIDER: S-EPMC8724292 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature