Title:Xanthine Oxidase and Transforming Growth Factor Beta-activated Kinase 1: Potential Targets for Gout Intervention
Volume: 17
Issue: 2
Author(s): Rajesh Basnet*, Sandhya Khadka, Buddha Bahadur Basnet, Til Bahadur Basnet, Buddhi Bal Chidi, Sanjeev Nirala, Radheshyam Gupta and Bidur Sharma
Affiliation:
- State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou,China
Keywords:
Gout, pathogenesis, clinical manifestation, XO, TAK1, inhibitor.
Abstract: Background: Gout, inflammatory arthritis caused by the deposition of monosodium
urate crystals into affected joints and other tissues, has become one of the major health problems of
today's world. The main risk factor for gout is hyperuricemia, which may be caused by excessive
or insufficient excretion of uric acid. The incidence is usually in the age group of 30- 50 years, commonly
in males. In developed countries, the incidence of gout ranges from 1 to 4%. Despite effective
treatments, there has been an increase in the number of cases over the past few decades.
Objective: In recent years, the development of targeted drugs in gout has made significant achievements.
The global impact of gout continues to increase, and as a result, the focus of disease-modifying
therapies remains elusive. In addition, the characterization of available instrumental compounds
is urgently needed to explore the use of novel selective and key protein-ligand interactions
for the effective treatment of gout. Xanthine oxidase (XO) is a key target in gout to consider the
use of XO inhibitors in patients with mild to moderate condition, however, the costs are high, and
no other direct progress has been made. Despite many XO inhibitors, a selective potent inhibitor
for XO is limited. Likewise, in recent years, attention has been focused on different strategies for
the discovery and development of new selectivity ligands against transforming growth factor beta-
activated kinase 1 (TAK1), a potential therapeutic target for gout. Therefore, the insight on human
XO structure and TAK1 provides a clue into protein-ligand interactions and provides the basis
for molecular modeling and structure-based drug design.
Conclusion: In this review, we briefly introduce the clinical characteristics, the development of
crystal, inhibitors, and crystal structure of XO and TAK1 protein.
