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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Published:2022-02
Issue:2
Volume:21
Page:188-205
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ISSN:1871-5273
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Container-title:CNS & Neurological Disorders - Drug Targets
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language:en
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Short-container-title:CNSNDDT
Author:
Tolomeu Heber Victor1,
Fraga Carlos Alberto Manssour1
Affiliation:
1. Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, RJ,Brazil
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.
Funder
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior -Brasil
INCT-INOFAR
CNPq
FAPERJ
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,General Neuroscience
Cited by
2 articles.
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