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FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.

作者信息

Lui Austin, Vanleuven Jordan, Perekopskiy David, Liu Dewey, Xu Desiree, Alzayat Omar, Elgokhy Taiseer, Do Timothy, Gann Meghan, Martin Ryan, Liu Da-Zhi

机构信息

Department of Neurology, University of California at Davis, Davis, CA 95618, USA.

Department of Neurological Surgery and Neurology, University of California at Davis, Davis, CA 95618, USA.

出版信息

Pharmaceuticals (Basel). 2022 Dec 13;15(12):1546. doi: 10.3390/ph15121546.


DOI:10.3390/ph15121546
PMID:36558997
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9784968/
Abstract

Cancers and neurological disorders are two major types of diseases. We previously developed a new concept termed "Aberrant Cell Cycle Diseases" (ACCD), revealing that these two diseases share a common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncogene activation and tumor suppressor inactivation, which are hallmarks of tumor growth in cancers and neuronal death in neurological disorders. Therefore, some cancer therapies (e.g., kinase inhibition, tumor suppressor elevation) can be leveraged for neurological treatments. The United States Food and Drug Administration (US FDA) has so far approved 74 kinase inhibitors, with numerous other kinase inhibitors in clinical trials, mostly for the treatment of cancers. In contrast, there are dire unmet needs of FDA-approved drugs for neurological treatments, such as Alzheimer's disease (AD), intracerebral hemorrhage (ICH), ischemic stroke (IS), traumatic brain injury (TBI), and others. In this review, we list these 74 FDA-approved kinase-targeted drugs and identify those that have been reported in preclinical and/or clinical trials for neurological disorders, with a purpose of discussing the feasibility and applicability of leveraging these cancer drugs (FDA-approved kinase inhibitors) for neurological treatments.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a39a/9784968/2e99c16127c1/pharmaceuticals-15-01546-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a39a/9784968/2e99c16127c1/pharmaceuticals-15-01546-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a39a/9784968/2e99c16127c1/pharmaceuticals-15-01546-g001.jpg

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引用本文的文献

[1]
Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).

Explor Drug Sci. 2025

[2]
Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain.

Exp Neurol. 2024-12

[3]
Tumor Suppressor MicroRNAs in Clinical and Preclinical Trials for Neurological Disorders.

Pharmaceuticals (Basel). 2024-3-27

[4]
Application of parallel artificial membrane permeability assay technique and chemometric modeling for blood-brain barrier permeability prediction of protein kinase inhibitors.

Future Med Chem. 2024

[5]
Mapping the substrate landscape of protein phosphatase 2A catalytic subunit PPP2CA.

iScience. 2024-2-19

[6]
PROTAC chemical probes for histone deacetylase enzymes.

RSC Chem Biol. 2023-7-27

[7]
Profiling tyrosine kinase inhibitors as AD therapeutics in a mouse model of AD.

Mol Brain. 2023-8-14

本文引用的文献

[1]
A motor neuron disease mouse model reveals a non-canonical profile of senescence biomarkers.

Dis Model Mech. 2022-8-1

[2]
Delay of endothelial cell senescence protects cerebral barrier against age-related dysfunction: role of senolytics and senomorphics.

Tissue Barriers. 2023-7-3

[3]
P97/VCP ATPase inhibitors can rescue p97 mutation-linked motor neuron degeneration.

Brain Commun. 2022-7-6

[4]
Foresee Novel Targets for Alzheimer's Disease by Investigating Repurposed Drugs.

CNS Neurol Disord Drug Targets. 2023

[5]
Rapamycin Attenuates Anxiety and Depressive Behavior Induced by Helicobacter pylori in Association with Reduced Circulating Levels of Ghrelin.

Neural Plast. 2022

[6]
Neuroprotection of Everolimus Against Focal Cerebral Ischemia-Reperfusion Injury in Rats.

J Stroke Cerebrovasc Dis. 2022-8

[7]
Combined induction of mTOR-dependent and mTOR-independent pathways of autophagy activation as an experimental therapy for Alzheimer's disease-like pathology in a mouse model.

Pharmacol Biochem Behav. 2022-6

[8]
The neuronal tyrosine kinase receptor ligand ALKAL2 mediates persistent pain.

J Clin Invest. 2022-6-15

[9]
Novel use of FDA-approved drugs identified by cluster analysis of behavioral profiles.

Sci Rep. 2022-4-21

[10]
c-Abl Activation Linked to Autophagy-Lysosomal Dysfunction Contributes to Neurological Impairment in Niemann-Pick Type A Disease.

Front Cell Dev Biol. 2022-3-18

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