Discovery of ZJCK-6-46: A Potent, Selective, and Orally Available Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitor for the Treatment of Alzheimer’s Disease-Reference-Cited by-同舟云学术

Discovery of ZJCK-6-46: A Potent, Selective, and Orally Available Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitor for the Treatment of Alzheimer’s Disease

Published:2024-07-23 Issue:15 Volume:67 Page:12571-12600
ISSN:0022-2623
Container-title:Journal of Medicinal Chemistry
language:en
Short-container-title:J. Med. Chem.

Author:

Chen Huanhua¹,Gao Xudong²,Li Xinzhu³,Yu Chong¹,Liu Wenwu¹,Qiu Jingsong¹,Liu Wenjie¹,Geng Hefeng³,Zheng Fangyuan³,Gong Hao¹,Xu Zihua¹,Jia Jingming¹,Zhao Qingchun¹³²^ORCID

Affiliation:

1. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road Shenhe District, Shenyang, Liaoning 110016, P. R. China

2. Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, China

3. School of Life Science and Biochemistry, Shenyang Pharmaceutical University, 103 Wenhua Road Shenhe District, Shenyang, Liaoning 110016, P. R. China

Funder

Natural Science Foundation of Liaoning Province

National Natural Science Foundation of China

Shenyang Municipal Bureau of Science and Technology

Publisher

American Chemical Society (ACS)

Link

https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.4c00483

Reference65 articles.

1. DYRK protein kinases

2. The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between β-amyloid production and tau phosphorylation in Alzheimer disease

3. Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer’s disease

4. Normalizing the gene dosage of Dyrk1A in a mouse model of Down syndrome rescues several Alzheimer's disease phenotypes

5. DYRK1A antagonists rescue degeneration and behavioural deficits of in vivo models based on amyloid-β, Tau and DYRK1A neurotoxicity