6S1I

Crystal Structure of DYRK1A with small molecule inhibitor

Summary for 6S1I

• Entry DOI: 10.2210/pdb6s1i/pdb
• Descriptor: Dual specificity tyrosine-phosphorylation-regulated kinase 1A, SULFATE ION, TETRAETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: kinase, catalytic domain, phosphorylated, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 171179.04

Authors

Sorrell, F.J.,Henderson, S.H.,Redondo, C.,Burgess-Brown, N.A.,von Delft, F.,Arrowsmith, C.H.,Bountra, C.,Edwards, A.M.,Elkins, J.M. (deposition date: 2019-06-18, release date: 2019-06-26, Last modification date: 2024-01-24)

Primary citation

Henderson, S.H.,Sorrell, F.,Bennett, J.,Hanley, M.T.,Robinson, S.,Hopkins Navratilova, I.,Elkins, J.M.,Ward, S.E.
Mining Public Domain Data to Develop Selective DYRK1A Inhibitors.
Acs Med.Chem.Lett., 11:1620-1626, 2020

PubMed Abstract: Kinases represent one of the most intensively pursued groups of targets in modern-day drug discovery. Often it is desirable to achieve selective inhibition of the kinase of interest over the remaining ∼500 kinases in the human kinome. This is especially true when inhibitors are intended to be used to study the biology of the target of interest. We present a pipeline of open-source software that analyzes public domain data to repurpose compounds that have been used in previous kinase inhibitor development projects. We define the dual-specificity tyrosine-regulated kinase 1A (DYRK1A) as the kinase of interest, and by addition of a single methyl group to the chosen starting point we remove glycogen synthase kinase β (GSK3β) and cyclin-dependent kinase (CDK) inhibition. Thus, in an efficient manner we repurpose a GSK3β/CDK chemotype to deliver , a highly selective DYRK1A inhibitor.

PubMed: 32832032
DOI: 10.1021/acsmedchemlett.0c00279

Experimental method

X-RAY DIFFRACTION (2.38 Å)