"目录号: HY-15258
Membrane Transporter/Ion Channel-
Lesinurad 是一种URAT1和OAT抑制剂，用作肾转运蛋白OAT1 和OAT3 的底物，Km值分别为 0.85 和 2 μM。
URAT1
相关产品
Lesinurad sodium-Verinurad-
生物活性
Description
Lesinurad is aURAT1andOATinhibitor, is determined to be a substrate for the kidney transportersOAT1andOAT3withKmvalues of 0.85 and 2 μM, respectively.
IC50& Target
Km: 0.85 μM (OAT1), 2 μM (OAT3)[1]
In Vitro
Lesinurad is a novel selective uric acid reabsorption inhibitor (SURI). Lesinurad is determined to be a substrate for the kidney transporters organic anion transporter (OAT1) and OAT3 with Kmvalues of 0.85 and 2 μM, respectively[1]. Lesinurad (RDEA594) is a URAT1 and OAT inhibitor, which increases proximal renal tubule urate excretion[2]. Lesinurad (RDEA594) is a potential uric acid lowering agent througn inhibition of uric acid reuptake, and exhibits favorable p450 profiles, inhibits CYP2C9 and CYP2C8 with IC50of 14.4 μM and 16.2 μM, respectively. IC50s of Lesinurad are all above 100 μM for CYP1A2, CYP2C19,and CYP2D6[3].
In Vivo
Lesinurad (RDEA594) shows better pharmacokinetics than its pro-drug RDEA806. The 100 mg dose of Lesinurad exhibits a phamacological effect in the range of that produced by 300 mg to 800 mg single doses of RDEA806[3].
Clinical Trial
NCT02039700
Ardea Biosciences, Inc.
Healthy
January 2014
Phase 1
NCT02127775
Ardea Biosciences, Inc.
Healthy
April 2014
Phase 1
NCT01908257
Ardea Biosciences, Inc.
Healthy
July 2013
Phase 1
NCT01986556
Ardea Biosciences, Inc.
Healthy
November 2013
Phase 1
NCT03226899
Ironwood Pharmaceuticals, Inc.-Medpace, Inc.
Gout-Chronic Kidney Disease (CKD)
July 19, 2017
Phase 4
NCT01808131
Ardea Biosciences, Inc.
Gout
February 2013
Phase 3
NCT01808144
Ardea Biosciences, Inc.
Gout
March 2013
Phase 3
NCT01650246
Ardea Biosciences, Inc.
Gout
August 2012
Phase 3
NCT01508702
Ardea Biosciences, Inc.
Gout
January 2012
Phase 3
NCT02888054
Ardea Biosciences, Inc.
Healthy
August 30, 2016
Phase 1
NCT01982201
Ardea Biosciences, Inc.
Healthy
November 2013
Phase 1
NCT01493531
Ardea Biosciences, Inc.
Gout
December 2011
Phase 3
NCT01510769
Ardea Biosciences, Inc.
Tophaceous Gout
January 2012
Phase 3
NCT01884272
Ardea Biosciences, Inc.
Gout
June 2013
Phase 1
NCT02581553
Ardea Biosciences, Inc.
Healthy
October 2015
Phase 1
NCT01744379
Ardea Biosciences, Inc.
Gout
December 2012
Phase 1
NCT01510158
Ardea Biosciences, Inc.
Gout
January 2012
Phase 3
NCT02028689
Ardea Biosciences, Inc.
Healthy
October 2013
Phase 1
NCT01001338
Ardea Biosciences, Inc.
Gout
October 2009
Phase 2
NCT00955981
Ardea Biosciences, Inc.
Hyperuricemia
July 2009
Phase 2
View MoreCollapse
References
[1].Shen Z, et al. In Vitro and In Vivo Interaction Studies Between Lesinurad, a Selective Urate Reabsorption Inhibitor, and Major Liver or Kidney Transporters. Clin Drug Investig. 2016 Jun;36(6):443-52.
[2].Sattui SE, et al. Treatment of hyperuricemia in gout: current therapeutic options, latest developments and clinical implications. Ther Adv Musculoskelet Dis. 2016 Aug;8(4):145-59.
[3].L.Yeh, et al. RDEA594, a potential uric acid lowering agent througn inhibition of uric acid reuptake ,shows better pharmacokinetics rhan its prodrug RDEA806. 2008 ACR/ARHP Annual Scientific Meeting, 24-29 October 2008, USA.