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Xanthine Oxidase and Transforming Growth Factor Beta-activated Kinase 1: Potential Targets for Gout Intervention

[ Vol. 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   Pages 153 - 161 ( 9 )

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.

Keywords:

Gout, pathogenesis, clinical manifestation, XO, TAK1, inhibitor.

Affiliation:

State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Department of Pharmacy, Hope International College, Purbanchal University, Lalitpur, Faculty of Science, Nepal Academy of Science and Technology, Lalitpur, Little Buddha College of Health Sciences, Purbanchal University, Min Bhawan Kathmandu, Department of Drug Administration, Government of Nepal, Kathmandu, Department of Cardiology of the Ruijin Hospital affiliated to the Shanghai Jiaotong University School of Medicine, Shanghai, Dept. of General Surgery, Bariatric and Metabolic Surgery, Nepal Korea Friendship Municipality Hospital, Madhyapur Thimi, Nepal, Qiqihar Medical University, Heilongjiang, Department of Pharmacy, School of Science, Kathmandu University, Dhulikhel

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