SGC-CLK-1: A chemical probe for the Cdc2-like kinases CLK1, CLK2, and CLK4.
CLK1
CLK2
CLK4
Chemical probe
Splicing
Journal
Current research in chemical biology
ISSN: 2666-2469
Titre abrégé: Curr Res Chem Biol
Pays: Netherlands
ID NLM: 9918434484806676
Informations de publication
Date de publication:
2023
2023
Historique:
medline:
27
11
2023
pubmed:
27
11
2023
entrez:
27
11
2023
Statut:
ppublish
Résumé
Small molecule modulators are important tools to study both basic biology and the complex signaling of protein kinases. The cdc2-like kinases (CLK) are a family of four kinases that have garnered recent interest for their involvement in a diverse set of diseases such as neurodegeneration, autoimmunity, and many cancers. Targeted medicinal chemistry around a CLK inhibitor hit identified through screening of a kinase inhibitor set against a large panel of kinases allowed us to identify a potent and selective inhibitor of CLK1, 2, and 4. Here, we present the synthesis, selectivity, and preliminary biological characterization of this compound - SGC-CLK-1 (CAF-170). We further show CLK2 has the highest binding affinity, and high CLK2 expression correlates with a lower IC
Identifiants
pubmed: 38009092
doi: 10.1016/j.crchbi.2023.100045
pmc: PMC10673624
mid: NIHMS1942723
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : K99 CA279896
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS115403
Pays : United States
Organisme : NCI NIH HHS
ID : K00 CA234799
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS125318
Pays : United States
Organisme : NCATS NIH HHS
ID : R44 TR001916
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS122375
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK116204
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS126810
Pays : United States
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