7A53

Structure of DYRK1A in complex with compound 7

Summary for 7A53

• Entry DOI: 10.2210/pdb7a53/pdb
• Related: 7a4o 7a4r 7a4s 7a4w 7a4z 7a51 7a52
• Descriptor: Dual specificity tyrosine-phosphorylation-regulated kinase 1A, (3~{E})-3-[(5-methylfuran-2-yl)methylidene]-1~{H}-indol-2-one (3 entities in total)
• Functional Keywords: serine/threonine-protein kinase, phosphoprotein, kinase, sbdd, fbld, small molecule inhibitor, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 83744.74

Authors

Dokurno, P.,Surgenor, A.E.,Hubbard, R.E. (deposition date: 2020-08-20, release date: 2021-06-30, Last modification date: 2024-11-06)

Primary citation

Lee Walmsley, D.,Murray, J.B.,Dokurno, P.,Massey, A.J.,Benwell, K.,Fiumana, A.,Foloppe, N.,Ray, S.,Smith, J.,Surgenor, A.E.,Edmonds, T.,Demarles, D.,Burbridge, M.,Cruzalegui, F.,Kotschy, A.,Hubbard, R.E.
Fragment-Derived Selective Inhibitors of Dual-Specificity Kinases DYRK1A and DYRK1B.
J.Med.Chem., 64:8971-8991, 2021

PubMed Abstract: The serine/threonine kinase DYRK1A has been implicated in regulation of a variety of cellular processes associated with cancer progression, including cell cycle control, DNA damage repair, protection from apoptosis, cell differentiation, and metastasis. In addition, elevated-level DYRK1A activity has been associated with increased severity of symptoms in Down's syndrome. A selective inhibitor of DYRK1A could therefore be of therapeutic benefit. We have used fragment and structure-based discovery methods to identify a highly selective, well-tolerated, brain-penetrant DYRK1A inhibitor which showed in vivo activity in a tumor model. The inhibitor provides a useful tool compound for further exploration of the effect of DYRK1A inhibition in models of disease.

PubMed: 34143631
DOI: 10.1021/acs.jmedchem.1c00024

Experimental method

X-RAY DIFFRACTION (2.2 Å)