SB-242235, a selective inhibitor of p38 mitogenactivated protein kinase. I: Preclinical pharmacokinetics

Xenobiotica ◽  
2002 ◽  
Vol 32 (3) ◽  
pp. 221-233 ◽  
Author(s):  
K. W. Ward ◽  
J. W. Proksch ◽  
K. L. Salyers ◽  
L. M. Azzarano ◽  
J. A. Morgan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Selective Inhibitor ◽  
Preclinical Pharmacokinetics ◽  
Mitogenactivated Protein Kinase

A novel DYRK1B inhibitor AZ191 demonstrates that DYRK1B acts independently of GSK3β to phosphorylate cyclin D1 at Thr286, not Thr288

2013 ◽  
Vol 457 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Anne L. Ashford ◽  
David Oxley ◽  
Jason Kettle ◽  
Kevin Hudson ◽  
Sylvie Guichard ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclin D1 ◽  
Selective Inhibitor ◽  
First Time

We use AZ191, a novel selective inhibitor of the DYRK1B protein kinase to show for the first time that DYRK1B acts independently of GSK3β to phosphorylate CCND1 (cyclin D1) at Thr286 (not Thr288 as previously suggested), thereby promoting CCND1 turnover.

scholarly journals Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase

2014 ◽  
Vol 463 (3) ◽  
pp. 413-427 ◽  
Author(s):  
Ruzica Bago ◽  
Nazma Malik ◽  
Michael J. Munson ◽  
Alan R. Prescott ◽  
Paul Davies ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Selective Inhibitor ◽  
Class Iii ◽  
Phosphate Binding ◽  
Downstream Target ◽  
Phosphoinositide 3 Kinase ◽  
Phosphatidylinositol 3

We characterize VPS34-IN, a potent and selective inhibitor of class III Vps34 PI3K. Using VPS34-IN1, we demonstrate that PtdIns(3)P, produced by Vps34 controls phosphorylation and activity of the SGK3 protein kinase.

scholarly journals Validation of the protein kinase PfCLK3 as a multistage cross-species malarial drug target

Science ◽  
2019 ◽  
Vol 365 (6456) ◽  
pp. eaau1682 ◽  
Author(s):  
Mahmood M. Alam ◽  
Ana Sanchez-Azqueta ◽  
Omar Janha ◽  
Erika L. Flannery ◽  
Amit Mahindra ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Protein Kinase ◽  
Rna Splicing ◽  
Drug Target ◽  
Selective Inhibitor ◽  
Molecular Pathways ◽  
Life Stages ◽  
Next Generation ◽  
Down Regulation ◽  
Transmission Blocking

The requirement for next-generation antimalarials to be both curative and transmission-blocking necessitates the identification of previously undiscovered druggable molecular pathways. We identified a selective inhibitor of the Plasmodium falciparum protein kinase PfCLK3, which we used in combination with chemogenetics to validate PfCLK3 as a drug target acting at multiple parasite life stages. Consistent with a role for PfCLK3 in RNA splicing, inhibition resulted in the down-regulation of more than 400 essential parasite genes. Inhibition of PfCLK3 mediated rapid killing of asexual liver- and blood-stage P. falciparum and blockade of gametocyte development, thereby preventing transmission, and also showed parasiticidal activity against P. berghei and P. knowlesi. Hence, our data establish PfCLK3 as a target for drugs, with the potential to offer a cure—to be prophylactic and transmission blocking in malaria.

OK-1035, a Selective Inhibitor of DNA-Dependent Protein Kinase

1995 ◽  
Vol 215 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Y. Take ◽  
M. Kumano ◽  
Y. Hamano ◽  
H. Fukatsu ◽  
H. Teraoka ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Selective Inhibitor ◽  
Dependent Protein Kinase ◽  
Dependent Protein
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