Current and Emerging Therapies for Gout

Mohammad, Samya; Giattino, Stephanie L.; Keenan, Robert T.

doi:10.1007/s40674-015-0015-6

Cited by 5 publications

(2 citation statements)

References 51 publications

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“…Gout attacks, for example, are more pronounced during the rest (night/dark) period and are likely related to uric acid metabolism ( 81 ). Interestingly, genes such as xanthine dehydrogenase ( Xdh ) and urate oxidase ( Uox ), which are critical for clearing uric acid, have also been recognized as pharmacologic targets ( 82 ). Hyperuricemia drives acute gout flares.…”

Section: Rhythms Of Homeostasis and Therapeuticsmentioning

confidence: 99%

Circadian Effects of Drug Responses

Nahmias

Androulakis

2021

Annu. Rev. Biomed. Eng.

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Circadian rhythms describe physiological systems that repeat themselves with a cycle of approximately 24 h. Our understanding of the cellular and molecular origins of these oscillations has improved dramatically, allowing us to appreciate the significant role these oscillations play in maintaining physiological homeostasis. Circadian rhythms allow living organisms to predict and efficiently respond to a dynamically changing environment, set by repetitive day/night cycles. Since circadian rhythms underlie almost every aspect of human physiology, it is unsurprising that they also influence the response of a living organism to disease, stress, and therapeutics. Therefore, not only do the mechanisms that maintain health and disrupt homeostasis depend on our internal circadian clock, but also the way drugs are perceived and function depends on these physiological rhythms. We present a holistic view of the therapeutic process, discussing components such as disease state, pharmacokinetics, and pharmacodynamics, as well as adverse reactions that are critically affected by circadian rhythms. We outline challenges and opportunities in moving toward personalized medicine approaches that explore and capitalize on circadian rhythms for the benefit of the patient. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: Rhythms Of Homeostasis and Therapeuticsmentioning

confidence: 99%

Circadian Effects of Drug Responses

Nahmias

Androulakis

2021

Annu. Rev. Biomed. Eng.

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“…Used optimally these three ULT alternatives are likely to provide effective serum urate control in the majority of cases. There are a number of ULT agents under development, which include lesinurad (selective inhibitor of the URAT1 transporter in the distal renal tubule), RLBN1001 (mixed actions of moderate XOI and potent inhibitor of URAT1) and arhalofenate (a uricosuric agent with possible anti‐inflammatory actions), which may ultimately provide alternative strategies for ULT suitable for all patients …”

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confidence: 99%

Rules of engagement: turning recommendations into results in the diagnosis and management of gout

Grainger

Harrison

2015

Int J of Rheum Dis

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Discovery of a Novel Inhibitor of Human Purine Nucleoside Phosphorylase by a Simple Hydrophilic Interaction Liquid Chromatography Enzymatic Assay

Rabuffetti

Rinaldi

Bianco³

et al. 2021

ChemMedChem

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Human purine nucleoside phosphorylase (HsPNP) belongs to the purine salvage pathway of nucleic acids. Genetic deficiency of this enzyme triggers apoptosis of activated T-cells due to the accumulation of deoxyguanosine triphosphate (dGTP). Therefore, potential chemotherapeutic applications of human PNP inhibitors include the treatment of T-cell leukemia, autoimmune diseases and transplant tissue rejection. In this report, we present the discovery of novel HsPNP inhibitors by coupling experimental and computational tools. A simple, inexpensive, direct and non-radioactive enzymatic assay coupled to hydrophilic interaction liquid chromatography and UV detection (LC-UV using HILIC as elution mode) was developed for screening HsPNP inhibitors. Enzymatic activity was assessed by monitoring the phosphorolysis of inosine (Ino) to hypoxanthine (Hpx) by LC-UV. A small library of 6-and 8-substituted nucleosides was synthesized and screened. The inhibition potency of the most promising compound, 8-aminoinosine (4), was quantified through K i and IC 50 determinations. The effect of HsPNP inhibition was also evaluated in vitro through the study of cytotoxicity on human T-cell leukemia cells (CCRF-CEM). Docking studies were also carried out for the most potent compound, allowing further insights into the inhibitor interaction at the HsPNP active site. This study provides both new tools and a new lead for developing novel HsPNP inhibitors.

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Current and Emerging Therapies for Gout

Cited by 5 publications

References 51 publications

Circadian Effects of Drug Responses

Circadian Effects of Drug Responses

Rules of engagement: turning recommendations into results in the diagnosis and management of gout

Discovery of a Novel Inhibitor of Human Purine Nucleoside Phosphorylase by a Simple Hydrophilic Interaction Liquid Chromatography Enzymatic Assay

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