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Current Rheumatology Reviews

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ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

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Review Article

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

Author(s): Rajesh Basnet*, Sandhya Khadka, Buddha Bahadur Basnet, Til Bahadur Basnet, Buddhi Bal Chidi, Sanjeev Nirala, Radheshyam Gupta and Bidur Sharma

Volume 17, Issue 2, 2021

Published on: 26 November, 2020

Page: [153 - 161] Pages: 9

DOI: 10.2174/1573397116666201126162202

Price: $65

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.

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[1]
Ragab G, Elshahaly M, Bardin T. Gout: An old disease in new perspective - A review. J Adv Res 2017; 8(5): 495-511.
[http://dx.doi.org/10.1016/j.jare.2017.04.008] [PMID: 28748116]
[2]
Zhang Q-B, Zhu D, Wen Z, et al. High levels of serum uric acid, Cystain C and lipids concentration and their clinical significance in primary gouty Arthritis patients. Curr Rheumatol Rev 2019; 15(2): 141-5.
[http://dx.doi.org/10.2174/1573397114666180705095625] [PMID: 29984668]
[3]
Dalbeth N, Merriman TR, Stamp LK. Gout. Lancet 2016; 388(10055): 2039-52.
[http://dx.doi.org/10.1016/S0140-6736(16)00346-9] [PMID: 27112094]
[4]
George J, Struthers AD. Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress. Vasc Health Risk Manag 2009; 5(1): 265-72.
[http://dx.doi.org/10.2147/VHRM.S4265] [PMID: 19436671]
[5]
Chen C, Lü J-M, Yao Q. Hyperuricemia-related diseases and xanthine oxidoreductase (XOR) inhibitors: an overview. Med Sci Monit 2016; 22: 2501-12.
[http://dx.doi.org/10.12659/MSM.899852] [PMID: 27423335]
[6]
Coburn BW, Mikuls TR. Treatment Options for Acute Gout. Fed Pract 2016; 33(1): 35-40.
[PMID: 30766136]
[7]
Burns CM, Wortmann RL. Latest evidence on gout management: what the clinician needs to know. Ther Adv Chronic Dis 2012; 3(6): 271-86.
[http://dx.doi.org/10.1177/2040622312462056] [PMID: 23342241]
[8]
Ruoff G, Edwards NL. Overview of Serum Uric Acid Treatment Targets in Gout: Why Less Than 6 mg/dL? Postgrad Med 2016; 128(7): 706-15.
[http://dx.doi.org/10.1080/00325481.2016.1221732] [PMID: 27558643]
[9]
Pham AQ, Doan A, Andersen M. Pyrazinamide-induced hyperuricemia P   T : a peer-reviewed journal for formulary management 2014; 39 (10 ): 695 -715 .
[10]
Weiner ID, Mitch WE, Sands JM. Urea and ammonia metabolism and the control of renal nitrogen excretion. Clin J Am Soc Nephrol 2015; 10(8): 1444-58.
[http://dx.doi.org/10.2215/CJN.10311013] [PMID: 25078422]
[11]
Perez-Ruiz F, Calabozo M, Pijoan JI, Herrero-Beites AM, Ruibal A. Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout. Arthritis Rheum 2002; 47(4): 356-60.
[http://dx.doi.org/10.1002/art.10511] [PMID: 12209479]
[12]
Hallie RB. Epidemiology of Gout: Perspectives from the Past. Curr Rheumatol Rev 2011; 7(2): 106-13.
[http://dx.doi.org/10.2174/157339711795305022]
[13]
Schumacher HR Jr. The pathogenesis of gout. Cleve Clin J Med 2008; 75(Suppl. 5): S2-4.
[http://dx.doi.org/10.3949/ccjm.75.Suppl_5.S2] [PMID: 18822468]
[14]
Towiwat P, Chhana A, Dalbeth N. The anatomical pathology of gout: a systematic literature review. BMC Musculoskelet Disord 2019; 20(1): 140-0.
[http://dx.doi.org/10.1186/s12891-019-2519-y] [PMID: 30935368]
[15]
Yavorskyy A, Hernandez-Santana A, McCarthy G, McMahon G. Detection of calcium phosphate crystals in the joint fluid of patients with osteoarthritis - analytical approaches and challenges. Analyst (Lond) 2008; 133(3): 302-18.
[http://dx.doi.org/10.1039/b716791a] [PMID: 18299743]
[16]
Maiuolo J, Oppedisano F, Gratteri S, Muscoli C, Mollace V. Regulation of uric acid metabolism and excretion. Int J Cardiol 2016; 213: 8-14.
[http://dx.doi.org/10.1016/j.ijcard.2015.08.109] [PMID: 26316329]
[17]
Jacobs CL, Stern PJ. An unusual case of gout in the wrist: the importance of monitoring medication dosage and interaction. A case report. Chiropr Osteopat 2007; 15(1): 16.
[http://dx.doi.org/10.1186/1746-1340-15-16] [PMID: 17922921]
[18]
Roddy E. Revisiting the pathogenesis of podagra: why does gout target the foot? J Foot Ankle Res 2011; 4(1): 13.
[http://dx.doi.org/10.1186/1757-1146-4-13] [PMID: 21569453]
[19]
Harris MD, Siegel LB, Alloway JA. Gout and hyperuricemia. Am Fam Physician 1999; 59(4): 925-34.
[PMID: 10068714]
[20]
Pittman JR, Bross MH. Diagnosis and management of gout. Am Fam Physician 1999; 59(7): 1799-1806, 1810.
[PMID: 10208700]
[21]
Martillo MA, Nazzal L, Crittenden DB. The crystallization of monosodium urate. Curr Rheumatol Rep 2014; 16(2): 400.
[http://dx.doi.org/10.1007/s11926-013-0400-9] [PMID: 24357445]
[22]
Krishnan RS, Rahini P. A Review on Gouty Arthritis. Research Journal of Pharmacy and Technology 2019; 12(11): 5583-8.
[http://dx.doi.org/10.5958/0974-360X.2019.00967.3]
[23]
Wiederkehr MR, Moe OW. Uric acid nephrolithiasis: a systemic metabolic disorder. Clin Rev Bone Miner Metab 2011; 9(3-4): 207-17.
[http://dx.doi.org/10.1007/s12018-011-9106-6] [PMID: 25045326]
[24]
Battelli MG, Polito L, Bortolotti M, Bolognesi A. Xanthine oxidoreductase-derived reactive species: physiological and pathological effects. Oxid Med Cell Longev 2016; 2016: 3527579.
[http://dx.doi.org/10.1155/2016/3527579]
[25]
Ojha R, Singh J, Ojha A, Singh H, Sharma S, Nepali K. An updated patent review: xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015). Expert Opin Ther Pat 2017; 27(3): 311-45.
[http://dx.doi.org/10.1080/13543776.2017.1261111] [PMID: 27841045]
[26]
Sattui SE, Gaffo AL. Treatment of hyperuricemia in gout: current therapeutic options, latest developments and clinical implications. Ther Adv Musculoskelet Dis 2016; 8(4): 145-59.
[http://dx.doi.org/10.1177/1759720X16646703] [PMID: 27493693]
[27]
Kang SM, Lim S, Song H, et al. Allopurinol modulates reactive oxygen species generation and Ca2+ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes. Eur J Pharmacol 2006; 535(1-3): 212-9.
[http://dx.doi.org/10.1016/j.ejphar.2006.01.013] [PMID: 16516885]
[28]
Pacher P, Nivorozhkin A, Szabó C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 2006; 58(1): 87-114.
[http://dx.doi.org/10.1124/pr.58.1.6] [PMID: 16507884]
[29]
Sánchez-Lozada LG, Tapia E, Bautista-García P, et al. Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome. Am J Physiol Renal Physiol 2008; 294(4): F710-8.
[http://dx.doi.org/10.1152/ajprenal.00454.2007] [PMID: 18216151]
[30]
Nakamura T, Murase T, Nampei M, et al. Effects of topiroxostat and febuxostat on urinary albumin excretion and plasma xanthine oxidoreductase activity in db/db mice. Eur J Pharmacol 2016; 780: 224-31.
[http://dx.doi.org/10.1016/j.ejphar.2016.03.055] [PMID: 27038523]
[31]
Elion GB. Uric acidSpringer. 1978; pp. 485-514.
[http://dx.doi.org/10.1007/978-3-642-66867-8_21]
[32]
Enroth C, Eger BT, Okamoto K, Nishino T, Nishino T, Pai EF. Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proc Natl Acad Sci USA 2000; 97(20): 10723-8.
[http://dx.doi.org/10.1073/pnas.97.20.10723] [PMID: 11005854]
[33]
Pauff JM, Cao H, Hille R. Substrate orientation and catalysis at the molybdenum site in xanthine oxidase: crystal structures in complex with xanthine and lumazine. J Biol Chem 2009; 284(13): 8760-7.
[http://dx.doi.org/10.1074/jbc.M804517200] [PMID: 19109252]
[34]
Totzke J, Gurbani D, Raphemot R, et al. a selective TAK1 inhibitor, broadens the therapeutic efficacy of TNF-α inhibition for cancer and autoimmune disease Cell chemical biology 2017; 24 (8 ): 1029 -39 .
[http://dx.doi.org/10.1016/j.chembiol.2017.07.011]
[35]
Shim J-H, Xiao C, Paschal AE, et al. TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev 2005; 19(22): 2668-81.
[http://dx.doi.org/10.1101/gad.1360605] [PMID: 16260493]
[36]
Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017; 2(1): 1-9.
[http://dx.doi.org/10.1038/sigtrans.2017.23]
[37]
Scarneo SA, Mansourati A, Eibschutz LS, et al. Genetic and pharmacological validation of TAK1 inhibition in macrophages as a therapeutic strategy to effectively inhibit TNF secretion. Sci Rep 2018; 8(1): 17058.
[http://dx.doi.org/10.1038/s41598-018-35189-7] [PMID: 30451876]
[38]
Muraoka T, Ide M, Morikami K, et al. Discovery of a potent and highly selective transforming growth factor beta receptor-associated kinase 1 (TAK1) inhibitor by structure based drug design (SBDD) Bioorganic & medicinal chemistry 2016; 24 (18 ): 4206 -17 .
[39]
Tan L, Nomanbhoy T, Gurbani D, et al. Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2). J Med Chem 2015; 58(1): 183-96.
[http://dx.doi.org/10.1021/jm500480k] [PMID: 25075558]
[40]
Shen S, Zhang Y, Zhang R, Gong X. Sarsasapogenin induces apoptosis via the reactive oxygen species-mediated mitochondrial pathway and ER stress pathway in HeLa cells. Biochem Biophys Res Commun 2013; 441(2): 519-24.
[http://dx.doi.org/10.1016/j.bbrc.2013.10.101] [PMID: 24383086]
[41]
Kashyap P, Muthusamy K, Niranjan M, Trikha S, Kumar S. Sarsasapogenin: A steroidal saponin from Asparagus racemosus as multi target directed ligand in Alzheimer’s disease. Steroids 2020; 153: 108529.
[http://dx.doi.org/10.1016/j.steroids.2019.108529] [PMID: 31672628]
[42]
Lim SM, Jeong JJ, Kang GD, Kim KA, Choi HS, Kim DH. Timosaponin AIII and its metabolite sarsasapogenin ameliorate colitis in mice by inhibiting NF-κB and MAPK activation and restoring Th17/Treg cell balance. Int Immunopharmacol 2015; 25(2): 493-503.
[http://dx.doi.org/10.1016/j.intimp.2015.02.016] [PMID: 25698557]

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