The Outcomes of Small-Molecule Kinase Inhibitors and the Role of
ROCK2 as a Molecular Target for the Treatment of Alzheimer's Disease

Heber    Victor    Tolomeu; Carlos    Alberto Manssour    Fraga

doi:10.2174/1871527320666210820092220

Abstract

Background: Alzheimer's disease is rapidly becoming a major threat to public health, with an increasing number of individuals affected as the world's population ages. In this sense, studies have been carried out aiming at the identification of new small-molecule kinase inhibitors useful for the treatment of Alzheimer's disease.

Objective: In the present study, we investigated the compounds developed as inhibitors of different protein kinases associated with the pathogenesis of Alzheimer's disease.

Methods: The applied methodology was the use of the Clarivate Analytics Integrity and ClinicalTrials. com databases. Moreover, we highlight ROCK2 as a promising target despite being little studied for this purpose. A careful structure-activity relationship analysis of the ROCK2 inhibitors was performed to identify important structural features and fragments for the interaction with the kinase active site, aiming to rationally design novel potent and selective inhibitors.

Results: We were able to notice some structural characteristics that could serve as the basis to better guide the rational design of new ROCK2 inhibitors as well as some more in-depth characteristics regarding the topology of the active site of both isoforms of these enzymes, thereby identifying differences that could lead to planning more selective compounds.

Conclusion: We hope that this work can be useful to update researchers working in this area, enabling the emergence of new ideas and a greater direction of efforts for designing new ROCK2 inhibitors to identify new therapeutic alternatives for Alzheimer's disease.

Keywords: Alzheimer’s disease, Neurodegenerative diseases, Kinase inhibitors, Rho kinase 2, ROCK2, ROCK2 inhibitor.

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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1871527320666210820092220	Print ISSN 1871-5273
Publisher Name Bentham Science Publisher	Online ISSN 1996-3181

CNS & Neurological Disorders - Drug Targets

The Outcomes of Small-Molecule Kinase Inhibitors and the Role of ROCK2 as a Molecular Target for the Treatment of Alzheimer's Disease

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