Development and therapeutic potential of adaptor-associated kinase 1 inhibitors in human multifaceted diseases

Xin, Xin; Wang, Yue; Zhang, Lele; Zhang, Dan; Sha, Leihao; Zhu, Zhiming; Huang, Xiaoyi; Mao, Wuyu; Zhang, Jifa

doi:10.1016/j.ejmech.2023.115102

Cited by 14 publications

(3 citation statements)

References 124 publications

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“…has been proposed as a potential drug target for treating various neurological disorders and preventing viral entry, where the kinase activity is the target for inhibition (Martinez-Gualda et al, 2021;Xin et al, 2023). In light of our findings, the non-enzymatic activities of AAK1 should also be taken into account.…”

Section: Discussionmentioning

confidence: 75%

“…The surprising independence of SEL-5 function on its kinase activity opens a new path for investigation with high relevance also for mammalian biology. AAK1 has been proposed as a potential drug target for treating various neurological disorders and preventing viral entry, where the kinase activity is the target for inhibition (Martinez-Gualda et al, 2021; Xin et al, 2023). In light of our findings, the non-enzymatic activities of AAK1 should also be taken into account.…”

Section: Discussionmentioning

confidence: 99%

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Caenorhabditis elegansSEL-5/AAK1 regulates cell migration and cell outgrowth independently of its kinase activity

Knop

Zounarová

Macůrková

2023

Preprint

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During Caenorhabditis elegans development multiple cells migrate long distances or extend processes to reach their final position and/or attain proper shape. Wnt signalling pathway stands out as one of the major coordinators of cell migration or cell outgrowth along the anterior-posterior body axis. Wnt signalling outcome is fine-tuned by various mechanisms including endocytosis. In this study we show that SEL-5, the C. elegans orthologue of mammalian AP2-associated kinase AAK1, acts together with the retromer complex as a positive regulator of EGL-20/Wnt signalling during the migration of QL neuroblast daughter cells. At the same time, SEL-5 in cooperation with the retromer complex is also required during excretory canal cell outgrowth in a Wnt-independent manner. Importantly, SEL-5 kinase activity is not required for its role in either neuronal migration or excretory cell outgrowth and neither of these processes is dependent on DPY-23/AP2M1 phosphorylation. While Wnt proteins do not significantly contribute to the excretory canal guidance, LIN-44/Wnt and LIN-17/Frizzled together generate a stop signal inhibiting further canal outgrowth.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Caenorhabditis elegansSEL-5/AAK1 regulates cell migration and cell outgrowth independently of its kinase activity

Knop

Zounarová

Macůrková

2023

Preprint

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“…In this mechanism, CK2 phosphorylates several specific proteins, including XRCC1 (X-ray repair cross complementing 1), XRCC4, MRE11 (meiotic recombination 11 homologue 1), and MDC1 (mediator of DNA damage checkpoint protein 1) (Figure ). ,− …”

Section: Structures and Biological Functions Of Ck2mentioning

confidence: 99%

Strategies of Targeting CK2 in Drug Discovery: Challenges, Opportunities, and Emerging Prospects

Chen

Wang

et al. 2023

J. Med. Chem.

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CK2 (casein kinase 2) is a serine/threonine protein kinase that is ubiquitous in eukaryotic cells and plays important roles in a variety of cellular functions, including cell growth, apoptosis, circadian rhythms, DNA damage repair, transcription, and translation. CK2 is involved in cancer pathogenesis and the occurrence of many diseases. Therefore, targeting CK2 is a promising therapeutic strategy. Although many CK2specific small-molecule inhibitors have been developed, only CX-4945 has progressed to clinical trials. In recent years, novel CK2 inhibitors have gradually become a research hotspot, which is expected to overcome the limitations of traditional inhibitors. Herein, we summarize the structure, biological functions, and disease relevance of CK2 and emphatically analyze the structure−activity relationship (SAR) and binding modes of small-molecule CK2 inhibitors. We also discuss the latest progress of novel strategies, providing insights into new drugs targeting CK2 for clinical practice.

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An amino-rich polymer-coated magnetic nanomaterial for ultra-rapid separation of phosphorylated peptides in the serum of Parkinson’s disease patients

Zhang,

Wang,

Luo

et al. 2024

Anal Bioanal Chem

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Development and therapeutic potential of adaptor-associated kinase 1 inhibitors in human multifaceted diseases

Cited by 14 publications

References 124 publications

Caenorhabditis elegansSEL-5/AAK1 regulates cell migration and cell outgrowth independently of its kinase activity

Caenorhabditis elegansSEL-5/AAK1 regulates cell migration and cell outgrowth independently of its kinase activity

Strategies of Targeting CK2 in Drug Discovery: Challenges, Opportunities, and Emerging Prospects

An amino-rich polymer-coated magnetic nanomaterial for ultra-rapid separation of phosphorylated peptides in the serum of Parkinson’s disease patients

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