Small Molecule Inhibitors of DYRK1A Identified by Computational and Experimental Approaches

Yoon, Hye Ree; Balupuri, Anand; Choi, Kwang-Eun; Kang, Nam Sook

doi:10.3390/ijms21186826

Cited by 11 publications

(12 citation statements)

References 60 publications

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“… 30 , 31 As a result of these findings, selective Dyrk1A inhibitors have emerged as an attractive drug target for a variety of diseases. 32 However, whether Dyrk1A is involved in the pathogenesis of depression, in particularly its potential role during cell death and signalling pathways, is not clearly understood. In the present study, with use of a bilaterally intracerebral injection of AAV‐miR‐211‐5p virus into the CA1 area of CUMS rats to overexpress miR‐211‐5p, we found that a significant reduction in Dyrk1A expression levels was observed, effects which paralleled the decreases in pro‐apoptotic proteins BAX, Caspase‐3 and Caspase‐9 levels along with an up‐regulation in the levels of the anti‐apoptotic protein, Bcl‐2.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of microRNA‐211‐5p on chronic stress‐induced neuronal apoptosis and depression‐like behaviours

Shen

Zhang

et al. 2021

J Cellular Molecular Medi

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Depression is a major psychiatric disorder associated with structural and functional changes within specific brain regions. [1][2][3] However, the underlying pathophysiological mechanisms involved in this disorder, and thus the potential for corresponding therapeutic strategies, are not fully understood. Previous evidence has indicated that stressful stimuliinduced modulators can contribute to cell apoptosis, which may then be a critical neural process involved in the progression of neuronal injury and consequent depression-like behaviours. [4][5][6] Apoptosis is a complicated process which plays a central role in controlling cell numbers and

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of microRNA‐211‐5p on chronic stress‐induced neuronal apoptosis and depression‐like behaviours

Shen

Zhang

et al. 2021

J Cellular Molecular Medi

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“…[ 10 , 11 , 12 , 19 , 35 ]. The level of activity of DYRK1A is of key importance for its physiological and pathological effects [ 24 , 36 , 37 ]. Hence, DYRK1A is regulated based on both gene expression and protein abundance (for reviews see [ 34 , 35 , 36 , 38 ]) with both low and high expression exerting significant effects on human diseases ( Table 1 ).…”

Section: Dyrk1a Expression and Enzymatic Activitymentioning

confidence: 99%

“…For the last 20 years, many studies have demonstrated that DYRK1A dosage and activity play a key role across a variety of human diseases ( Figure 3 ) [ 37 , 114 , 130 , 131 , 132 , 133 , 134 , 135 ]. Over the past decade, the development of novel treatments to regulate DYRK1A activity in cell models and mouse models has exploded.…”

Section: Dyrk1a a Target For The Patient’s Futurementioning

confidence: 99%

The Omnipresence of DYRK1A in Human Diseases

Deboever

Fistrovich

Hulme

et al. 2022

IJMS

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The increasing population will challenge healthcare, particularly because the worldwide population has never been older. Therapeutic solutions to age-related disease will be increasingly critical. Kinases are key regulators of human health and represent promising therapeutic targets for novel drug candidates. The dual-specificity tyrosine-regulated kinase (DYRKs) family is of particular interest and, among them, DYRK1A has been implicated ubiquitously in varied human diseases. Herein, we focus on the characteristics of DYRK1A, its regulation and functional role in different human diseases, which leads us to an overview of future research on this protein of promising therapeutic potential.

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“…Finally, a number of other selective inhibitors have been reported though structure-based discovery ( 119 – 123 ). From these advanced studies, it appears that we are close to identifying clinically viable compounds for multiple indications, including metabolic, neurologic, and oncologic disorders.…”

Section: Introductionmentioning

confidence: 99%

The chromosome 21 kinase DYRK1A: emerging roles in cancer biology and potential as a therapeutic target

et al. 2022

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Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a serine/threonine kinase that belongs to the DYRK family of proteins, a subgroup of the evolutionarily conserved CMGC protein kinase superfamily. Due to its localization on chromosome 21, the biological significance of DYRK1A was initially characterized in the pathogenesis of Down syndrome (DS) and related neurodegenerative diseases. However, increasing evidence has demonstrated a prominent role in cancer through its ability to regulate biologic processes including cell cycle progression, DNA damage repair, transcription, ubiquitination, tyrosine kinase activity, and cancer stem cell maintenance. DYRK1A has been identified as both an oncogene and tumor suppressor in different models, underscoring the importance of cellular context in its function. Here, we review mechanistic contributions of DYRK1A to cancer biology and its role as a potential therapeutic target.

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Small Molecule Inhibitors of DYRK1A Identified by Computational and Experimental Approaches

Cited by 11 publications

References 60 publications

Neuroprotective effects of microRNA‐211‐5p on chronic stress‐induced neuronal apoptosis and depression‐like behaviours

Neuroprotective effects of microRNA‐211‐5p on chronic stress‐induced neuronal apoptosis and depression‐like behaviours

The Omnipresence of DYRK1A in Human Diseases

The chromosome 21 kinase DYRK1A: emerging roles in cancer biology and potential as a therapeutic target

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