Casein Kinase 1δ Inhibitors as Promising Therapeutic Agents for Neurodegenerative Disorders

被引：14

作者：

Catarzi, Daniela ^{[1
]}

Varano, Flavia ^{[1
]}

Vigiani, Erica ^{[1
]}

Lambertucci, Catia ^{[2
]}

Spinaci, Andrea ^{[2
]}

Volpini, Rosaria ^{[2
]}

Colotta, Vittoria ^{[1
]}

机构：

[1] Univ Firenze, Dipartimento Neurosci Psicol Area Farmaco & Salut, Sez Farmaceut & Nutraceut, Via Ugo Schiff 6, I-50019 Sesto Fiorentino, Italy

[2] Univ Camerino, Scuola Sci Farmaco & Prod Salute, Via S Agostino 1, I-62032 Camerino, MC, Italy

来源：

CURRENT MEDICINAL CHEMISTRY | 2022年 / 29卷 / 27期

关键词：

Casein kinase 1 delta; casein kinase 1 delta inhibitors; neuroprotective agents; anticancer agents; small molecules; natural inhibitors; drug design; AMYOTROPHIC-LATERAL-SCLEROSIS; 1-DELTA/1-EPSILON CK1-DELTA/EPSILON INHIBITORS; CYCLIN-DEPENDENT KINASES; PROTEIN-KINASE; DELTA; ALZHEIMERS-DISEASE; POTENT INHIBITORS; IN-VITRO; BIOLOGICAL EVALUATION; MOLECULAR-MECHANISMS;

D O I：

10.2174/0929867329666220301115124

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Casein kinase 1 (CK1) belongs to the serine-threonine kinase family and is expressed in all eukaryotic organisms. At least six human isoforms of CK1 (termed alpha, gamma 1-3, delta and epsilon) have been cloned and characterized. CK1 delta isoform modulates several physiological processes, including DNA damage repair, circadian rhythm, cellular proliferation and apoptosis. Therefore, CK1 delta dysfunction may trigger diverse pathologies, such as cancer, inflammation and central nervous system disorders. Overexpression and aberrant activity of CK1 delta have been connected to hyperphosphorylation of key proteins implicated in the development of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases and Amyotrophic Lateral Sclerosis. Thus, CK1 delta inhibitors have attracted attention as potential drugs for these pathologies and several compounds have been synthesized or isolated from natural sources to be evaluated for their CK1 delta inhibitory activity. Here we report a comprehensive review on the development of CK1 delta inhibitors, with a particular emphasis on structure-activity relationships and computational studies, which provide useful insight for the design of novel inhibitors.

引用

页码：4698 / 4737

页数：40

共 145 条

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