TARGETING URAT 1 AND GLUT 9 FOR HYPERURICEMIA MANAGEMENT: IMPORTANCE OF PRECLINICAL EVALUATION

Abstract

Hyperuricemia is marked by elevated serum uric acid levels. It is the primary risk factor for gout and several related complications. Urate homeostasis involves balancing uric acid production and renal excretion. Urate transporters, such as urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), play crucial roles. Evidence suggests that dysfunction or genetic variation in these transporters contributes to abnormal urate accumulation and disease progression. This review summarises knowledge of uric acid metabolism, renal urate handling, and the physiological roles of URAT1 and GLUT9 in urate balance. It discusses the involvement of these transporters in hyperuricemia and gout, as well as therapeutic strategies targeting urate transporters, including uricosuric drugs and emerging transporter-specific inhibitors. The importance of preclinical evaluation using animal models and cell-based transporter assays for the discovery and development of novel antihyperuricemic agents is highlighted. Understanding the molecular mechanisms and pharmacological modulation of urate transporters may help develop more effective therapies for hyperuricemia and gout.