"目录号: HY-15258A

Membrane Transporter/Ion Channel-

Lesinurad sodium (RDEA594 sodium)是URAT1抑制剂。

URAT1

相关产品

Lesinurad-Verinurad-

生物活性

Description

Lesinurad sodium 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

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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.