Solute carrier family 22 member 12 (SLC22A12, URAT1) acts as a urate transporter to regulate urate levels in blood.

Lesinurad sodium
UR 1102


An overview of URAT1

Urate transporter 1 (URAT1) is a member of the organic anion transporter (OAT) family, originally cloned from the human kidneys and positioned at the top (brush edge) membrane of the proximal tubular cell of the kidney. URAT1 can mediate the absorption of acid, thus regulating the concentration of uric acid. The damage of URAT1 activities, whether due to polymorphism or drug interactions, may have toxicological consequences.

Inhibition of URAT1

Lesinurad is a new selective inhibitor of URAT1. It was identified as renal transporter of OAT and matrix of OAT. It also increases the excretion of proximal renal tubules, a potential uric acid reducing agent. And it can inhibit the absorption of uric acid, show good p450 profiles, and inhibit CYP2C9 and CYP2C8.

URAT1 and diseases

Uric acid is the final product of human purine metabolism. The level of uric acid is determined by the balance between the formation and excretion of uric acids in the organism. Uric acid in human body is mainly excreted by kidney, and the kidney mainly depends on the ion channel of renal proximal convoluted tubular transporters. In the known renal tubule uric acid transporter protein, the human uric acid anion exchanger (URAT1) and glucose transporter 9 (GLUT9) expressed in the renal cortex proximal tubule epithelial cells, are the key transporters that mediate the reabsorption of renal uric acid and maintain the steady state of blood and uric acid. Studies found that serum uric acid in uric acid calculus patients is significantly elevated, whereas urine excretion of uric acid did not change significantly. And the renal histological test confirmed that the expression of URAT1 protein in the proximal tubule epithelial cells of patients with uric acid calculus was increased. The results showed that the formation of uric acid calculus was closely related to renal uric acid metabolism, and suggested that the expression of URAT1 in renal proximal tubules might be an important molecular mechanism for the formation of hyperuricemia in patients with uric acid calculus.