Discovery of 2‐(1,2,4‐triazol‐3‐yl)pyridine <scp>KTD</scp>‐092 as a novel <scp>DYRK1A</scp> inhibitor
Abstract Dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A) is a protein kinase that is ubiquitously expressed in human tissues and acts as a master regulator of cell proliferation and differentiation. DYRK1A might be associated with Down syndrome (DS), Alzheimer's disease (AD), autism spectrum disorder (ASD), diabetes and other neurodegenerative diseases. In search of novel and selective DYRK1A inhibitor scaffold, KTD‐092 are validated as a hit for DYRK1A inhibition. KTD‐092 shows good stability under various liver microsomes, and markedly reduces tau phosphorylation in a human neuroblastoma cell in a concentration‐dependent manner. Molecular binding mode of KTD‐092 to DYRK1A is also proposed.
Authors
- Jin Sook Song (ORCID: https://orcid.org/0000-0001-8023-7769)
- Seong Hwan Kim
- Suk‐Ho Hong (ORCID: https://orcid.org/0000-0003-3934-8672)
- Rajath Cyriac
- Sunjoo Ahn (ORCID: https://orcid.org/0000-0002-6519-6492)
- Kwangho Lee (ORCID: https://orcid.org/0000-0003-0968-0455)
- Chaemi Lee (ORCID: https://orcid.org/0009-0001-9221-2910)
- Seohui Hwang
- Eun Hye Kim
- Hansol Choi (ORCID: https://orcid.org/0009-0009-9528-4002)
- Gyung Ja Choi (ORCID: https://orcid.org/0000-0003-1564-1487)
- Chong Hak Chae (ORCID: https://orcid.org/0009-0007-4351-2638)
Institutions
- Chungnam National University (KR)
- Korea Research Institute of Chemical Technology (KR)
- Korea University of Science and Technology (KR)
Publication Details
- Journal
- Bulletin of the Korean Chemical Society
- Published
- 2025-04-15
- DOI
- https://doi.org/10.1002/bkcs.70018
- Citations
- 1
- Primary Topic
- Down syndrome and intellectual disability research
- Type
- article
- Field-Weighted Citation Impact
- 1.88
Funders
- Korea Research Institute of Chemical Technology