PF-06651600, a Dual JAK3/TEC Family Kinase Inhibitor.
Animals
Antigens, CD
/ immunology
Antigens, Differentiation, T-Lymphocyte
/ immunology
CD8-Positive T-Lymphocytes
/ drug effects
Humans
Janus Kinase 3
/ antagonists & inhibitors
Killer Cells, Natural
/ drug effects
Lectins, C-Type
/ antagonists & inhibitors
Mice
Protein Kinase Inhibitors
/ pharmacology
Protein-Tyrosine Kinases
/ antagonists & inhibitors
Pyrimidines
/ pharmacology
Pyrroles
/ pharmacology
Journal
ACS chemical biology
ISSN: 1554-8937
Titre abrégé: ACS Chem Biol
Pays: United States
ID NLM: 101282906
Informations de publication
Date de publication:
21 06 2019
21 06 2019
Historique:
pubmed:
15
5
2019
medline:
15
2
2020
entrez:
15
5
2019
Statut:
ppublish
Résumé
PF-06651600 was developed as an irreversible inhibitor of JAK3 with selectivity over the other three JAK isoforms. A high level of selectivity toward JAK3 is achieved by the covalent interaction of PF-06651600 with a unique cysteine residue (Cys-909) in the catalytic domain of JAK3, which is replaced by a serine residue in the other JAK isoforms. Importantly, 10 other kinases in the kinome have a cysteine at the equivalent position of Cys-909 in JAK3. Five of those kinases belong to the TEC kinase family including BTK, BMX, ITK, RLK, and TEC and are also inhibited by PF-06651600. Preclinical data demonstrate that inhibition of the cytolytic function of CD8
Identifiants
pubmed: 31082193
doi: 10.1021/acschembio.9b00188
doi:
Substances chimiques
Antigens, CD
0
Antigens, Differentiation, T-Lymphocyte
0
CD69 antigen
0
Lectins, C-Type
0
PF-06651600
0
Protein Kinase Inhibitors
0
Pyrimidines
0
Pyrroles
0
Tec protein-tyrosine kinase
EC 2.7.1.-
Protein-Tyrosine Kinases
EC 2.7.10.1
JAK3 protein, human
EC 2.7.10.2
Janus Kinase 3
EC 2.7.10.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM