生物活性

• 靶点	URAT1 EC50:0.05μM

• 描述URAT1 (urate transporter 1) is a transporter critical for renal reabsorption of urate. Inactivating mutations of URAT1 lead to high FEUA (fractional excretion of uric acid) and hypouricemia (abnormally low sUA (serum uric acid) levels). Verinurad inhibits the transport activity of human URAT1 in a dose-dependent manner, at high potency with an IC₅₀ of 25 nM. And it's currently under evaluation for the treatment of gout which is caused by elevated serum urate levels. Verinurad inhibits the related URAT1 homologs OAT4 and OAT1 with approximately 200-fold lower affinity compared to URAT1 with IC₅₀ values of 5.9 µM and 4.6 µM, respectively. Therefore, verinurad is highly specific for URAT1. Moreover, human URAT1 has a 1,640-fold higher affinity for verinurad compared to rat URAT1 (IC₅₀ = 41 µM). Consistent with the in vitro inhibition of URAT1, treatment of healthy human volunteers with a single 40 mg dose of verinurad reduced the sUA by up to 60% and increased the FEUA in a dose-dependent manner with a half-maximal effective concentration in plasma of 22 nM^[3].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03118739	Hyperuricemia ... more >> Albuminuria Type 2 Diabetes Collapse <<	Phase 2	Completed	-	United States, California ... more >> Research Site Canyon Country, California, United States, 91351 Research Site Chula Vista, California, United States, 91911 Research Site Corona, California, United States, 92882 Research Site Escondido, California, United States, 92025 Research Site Lakewood, California, United States, 90805 Research Site Lincoln, California, United States, 95648 Research Site Los Angeles, California, United States, 90017 Research Site Los Angeles, California, United States, 90022 Research Site Los Angeles, California, United States, 90036 Research Site North Hollywood, California, United States, 91606 Research Site Oceanside, California, United States, 92056-4510 Research Site Orange, California, United States, 92868 Research Site Sacramento, California, United States, 95821 United States, Texas Research Site Houston, Texas, United States, 77058 Research Site Houston, Texas, United States, 77070 Research Site Pearland, Texas, United States, 77584 Research Site Sugar Land, Texas, United States, 77478 Research Site Webster, Texas, United States, 77598 Collapse <<
  NCT03316131	Asymptomatic Hyperuricemia	Phase 2	Completed	-	United States, California ... more >> Research Site Glendale, California, United States, 91206 United States, Maryland Research Site Baltimore, Maryland, United States, 21225 Collapse <<

• 参考文献

• [1] Shen Z, Gillen M, et al. Pharmacokinetics, pharmacodynamics, and tolerability of verinurad, a selective uric acid reabsorption inhibitor, in healthy adult male subjects. Drug Des Devel Ther. 2017 Jul 7;11:2077-2086.

  [2] Tan PK, Liu S, et al. Discovery and characterization of verinurad, a potent and specific inhibitor of URAT1 for the treatment of hyperuricemia and gout. Sci Rep. 2017 Apr 6;7(1):665.

  [3] Tan PK, Liu S, Gunic E, Miner JN. Discovery and characterization of verinurad, a potent and specific inhibitor of URAT1 for the treatment of hyperuricemia and gout. Sci Rep. 2017;7(1):665. Published 2017 Apr 6.