Crystallization and Inhibition of Monosodium Urate Monohydrate: Advances in Mechanistic Understanding and Perspectives for Gout Management

Abstract

Gout is a severe and prevalent pathological mineralization disorder characterized by hyperuricemia and recurrent arthritis, driven by deposition of urate crystals in joints and surrounding tissues. Clinical management of gout primarily targets inflammation and pain during acute attacks, as well as long-term urate-lowering therapy. Nevertheless, achieving optimal control of gout remains a significant clinical challenge. As a crystal-induced disease, gout is fundamentally driven by monosodium urate monohydrate (MSUM) crystals, which represent the critical nexus between hyperuricemia and inflammatory responses. This has drawn substantial research interest from both medical and crystallographic communities. Inhibiting MSUM crystallization has emerged as a promising therapeutic strategy for gout management. In recent years, research on gout from a crystallographic perspective has flourished. This review systematically summarizes the research progress in understanding MSUM crystallization and its influencing factors, as well as the screening and development of MSUM crystallization inhibitors. It specifically discusses the challenges faced by MSUM inhibitors during clinical translation and the corresponding optimization strategies, aiming to bridge the gap between laboratory research and clinical applications.