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Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney

Overview of attention for article published in Arthritis Research & Therapy, October 2016
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1 Facebook page

Citations

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81 Dimensions

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46 Mendeley
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Title
Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney
Published in
Arthritis Research & Therapy, October 2016
DOI 10.1186/s13075-016-1107-x
Pubmed ID
Authors

Jeffrey N. Miner, Philip K. Tan, David Hyndman, Sha Liu, Cory Iverson, Payal Nanavati, David T. Hagerty, Kimberly Manhard, Zancong Shen, Jean-Luc Girardet, Li-Tain Yeh, Robert Terkeltaub, Barry Quart

Abstract

Excess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout. sUA levels, fractional excretion of uric acid (FEUA), lesinurad plasma levels, and urinary excretion of lesinurad were measured in healthy volunteers treated with lesinurad. In addition, lesinurad, probenecid, and benzbromarone were compared in vitro for effects on urate transporters and the organic anion transporters (OAT)1 and OAT3, changes in mitochondrial membrane potential, and human peroxisome proliferator-activated receptor gamma (PPARγ) activity. After 6 hours, a single 200-mg dose of lesinurad elevated FEUA 3.6-fold (p < 0.001) and reduced sUA levels by 33 % (p < 0.001). At concentrations achieved in the clinic, lesinurad inhibited activity of URAT1 and OAT4 in vitro, did not inhibit GLUT9, and had no effect on ABCG2. Lesinurad also showed a low risk for mitochondrial toxicity and PPARγ induction compared to benzbromarone. Unlike probenecid, lesinurad did not inhibit OAT1 or OAT3 in the clinical setting. The pharmacodynamic effects and in vitro activity of lesinurad are consistent with inhibition of URAT1 and OAT4, major apical transporters for uric acid. Lesinurad also has a favorable selectivity and safety profile, consistent with an important role in sUA-lowering therapy for patients with gout.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 46 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 9 20%
Student > Ph. D. Student 9 20%
Researcher 6 13%
Student > Master 5 11%
Other 4 9%
Other 4 9%
Unknown 9 20%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 10 22%
Medicine and Dentistry 8 17%
Agricultural and Biological Sciences 7 15%
Biochemistry, Genetics and Molecular Biology 5 11%
Chemistry 3 7%
Other 2 4%
Unknown 11 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 October 2016.
All research outputs
#6,950,417
of 11,622,318 outputs
Outputs from Arthritis Research & Therapy
#1,131
of 1,602 outputs
Outputs of similar age
#134,069
of 259,011 outputs
Outputs of similar age from Arthritis Research & Therapy
#19
of 26 outputs
Altmetric has tracked 11,622,318 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,602 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 259,011 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 26 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.