Therapeutic potential of adenosine kinase inhibition-Revisited

Pharmacology Research & Perspectives
M F Jarvis

Abstract

Adenosine (ADO) is an endogenous protective regulator that restores cellular energy balance in response to tissue trauma. Extracellular ADO has a half-life of the order of seconds thus restricting its actions to tissues and cellular sites where it is released. Adenosine kinase (AK, ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20) is a cytosolic enzyme that is the rate-limiting enzyme controlling extracellular ADO concentrations. Inhibition of AK can effectively increase ADO extracellular concentrations at tissue sites where pathophysiological changes occur. Highly potent and selective nucleoside and non-nucleoside AK inhibitors were discovered in the late 1990s that showed in vivo effects consistent with the augmentation of the actions of endogenous ADO in experimental models of pain, inflammation, and seizure activity. These data supported clinical development of several AK inhibitors for the management of epilepsy and chronic pain. However, early toxicological data demonstrated that nucleoside and non-nucleoside chemotypes produced hemorrhagic microfoci in brain in an apparent ADO receptor-dependent fashion. An initial oral report of these important toxicological findings was presented at an international conference but a de...Continue Reading

References

Apr 1, 1989·The American Journal of Physiology·G H MöserA Deussen
Feb 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·J SpychalaB S Mitchell
Jun 27, 1996·European Journal of Pharmacology·K GolembiowskaJ Sawynok
Feb 24, 1997·Biochemical and Biophysical Research Communications·T McNallyD N Halbert
Dec 8, 1998·Biochemistry·I I MathewsS E Ealick
Mar 29, 2000·Biochemical Pharmacology·M Williams, M F Jarvis
Apr 3, 2001·Annual Review of Neuroscience·T V Dunwiddie, S A Masino
Jun 6, 2003·Progress in Neurobiology·Jana Sawynok, Xue Jun Liu
Jan 11, 2005·Current Topics in Medicinal Chemistry·Steve McGaraughtyRobert F Berman
Mar 7, 2006·Nature Reviews. Drug Discovery·Kenneth A Jacobson, Zhan-Guo Gao
Dec 13, 2006·Journal of Medicinal Chemistry·Steven W MuchmoreClarissa L Jakob
Jan 2, 2007·Bioorganic & Medicinal Chemistry·Mark A MatulenkoShripad S Bhagwat
May 5, 2012·Purinergic Signalling·Herbert ZimmermannNorbert Sträter
Mar 29, 2013·Nature Reviews. Drug Discovery·Jiang-Fan ChenBertil B Fredholm
Apr 18, 2013·Pharmacological Reviews·Detlev Boison
Apr 20, 2013·Clinical Pharmacology and Therapeutics·P Vicini, P H van der Graaf
Oct 23, 2015·Critical Care Medicine·David KöhlerPeter Rosenberger
Oct 27, 2016·Neuroscience·J Sawynok
Dec 22, 2015·Neuropharmacology·Kenneth A Jacobson, Christa E Müller
Jul 14, 2016·Journal of Medicinal Chemistry·Kiran S TotiKenneth A Jacobson
Sep 7, 2016·Bioorganic & Medicinal Chemistry·Meryem KöseChrista E Müller
Jul 25, 2017·Biochemical Pharmacology·Geoffrey Burnstock
Oct 11, 2017·Frontiers in Pharmacology·Geoffrey Burnstock

❮ Previous
Next ❯

Citations

Mar 19, 2020·Pain·Kenneth A JacobsonDaniela Salvemini
Apr 2, 2020·Expert Opinion on Drug Discovery·Diego Dal BenRosaria Volpini
Oct 20, 2020·Frontiers in Immunology·Hajer AounallahMichail Kotsyfakis
Nov 18, 2020·International Journal of Molecular Sciences·Carla Trapero, Mireia Martín-Satué
Dec 17, 2020·Frontiers in Pharmacology·Jonathan D GeigerDetlev Boison
Feb 20, 2021·Pharmacology & Therapeutics·Aleksandra SzopaPiotr Wlaź
Nov 19, 2020·Biochemical Pharmacology·Francesco Di VirgilioMichael Williams
Nov 9, 2020·Biochemical Pharmacology·Detlev Boison, Michael F Jarvis
Jun 21, 2021·Chemical Biology & Drug Design·Victor V ZhirnovVolodymyr S Brovarets

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Current Pharmaceutical Design
E A KowalukM F Jarvis
Expert Opinion on Investigational Drugs
E A Kowaluk, M F Jarvis
Current Topics in Medicinal Chemistry
Steve McGaraughtyRobert F Berman
Current Pharmaceutical Design
Arthur Gomtsyan, Chih Hung Lee
© 2021 Meta ULC. All rights reserved