Novel Efficient Multistage Lead Optimization Pipeline Experimentally Validated for DYRK1B Selective Inhibitors.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
27 10 2022
27 10 2022
Historique:
pubmed:
15
10
2022
medline:
29
10
2022
entrez:
14
10
2022
Statut:
ppublish
Résumé
In addition to general challenges in drug discovery such as the identification of lead compounds in time- and cost-effective ways, specific challenges also exist. Particularly, it is necessary to develop pharmacological inhibitors that effectively discriminate between closely related molecular targets. DYRK1B kinase is considered a valuable target for cancer-specific mono- or combination chemotherapy; however, the inhibition of its closely related DYRK1A kinase is not beneficial. Existing inhibitors target both kinases with essentially the same efficiency, and the unavailability of the DYRK1B crystal structure makes the discovery of DYRK1B-specific inhibitors even more challenging. Here, we propose a novel multi-stage compound discovery pipeline aimed at
Identifiants
pubmed: 36239428
doi: 10.1021/acs.jmedchem.2c00988
pmc: PMC9619999
doi:
Substances chimiques
Protein-Tyrosine Kinases
EC 2.7.10.1
Protein Kinase Inhibitors
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Ligands
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
13784-13792Références
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