URAT1 inhibitor 4

URAT1 inhibitor 4, a Lesinurad derivative, is a potent and orally active URAT1 inhibitor with an IC50 of 7.56 μM. URAT1 inhibitor 4 has higher in vivo urate-lowering efficacy than Lesinurad (HY-15258)[1].

Signaling Pathways >> Membrane Transporter/Ion Channel >> URAT1

Research Areas >> Metabolic Disease

IC50: 7.56 ± 0.52 μM (URAT1), 55.96 ± 10.38 μM (GLUT9)[1]

URAT1 inhibitor 4 (化合物 10) 抑制 URAT1 和 GLUT9，IC50 分别为 7.56 ± 0.52 μM 和 55.96 ± 10.38 μM[1]。

URAT1 inhibitor 4 (2 mg/kg；单次口服) 降低急性高尿酸血症模型小鼠血清尿酸水平[1]。 URAT1 inhibitor 4 (1000 mg/kg; 单次灌胃) 在小鼠急性毒性评估中比 Lesinurad 的存活率更高。 Animal Model: Kunming mice (acute hyperuricemia model)[1] Dosage: 2 mg/kg Administration: p.o.; single dosage Result: Decreased serum uric acid with an decrease ratio of 73.29%. Animal Model: Kunming mice[1] Dosage: 1000 mg/kg Administration: i.g.; single dosage Result: Survival rate was 100% after 7 days, while Lesinurad were 40% (male) and 20% (female).

[1]. Zhang J, et al. Design, synthesis and activity evaluation of novel lesinurad analogues containing thienopyrimidinone or pyridine substructure as human urate transporter 1 inhibitors. Eur J Med Chem. 2022 Dec 15;244:114816.