scholarly journals Novel Small Molecule Inhibitors of Protein Kinase D Suppress NF-kappaB Activation and Attenuate the Severity of Rat Cerulein Pancreatitis

2017 ◽  
Vol 8 ◽  
Author(s):  
Jingzhen Yuan ◽  
Tanya Tan ◽  
Meng Geng ◽  
Grace Tan ◽  
Chintan Chheda ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Protein Kinase D ◽  
Nf Kappab

Sa1480 Novel Small Molecule Inhibitors of Protein Kinase D Suppress NF-κB Activation in In Vitro and In Vivo Experimental Acute Pancreatitis

2016 ◽  
Vol 150 (4) ◽  
pp. S326-S327
Author(s):  
Jingzhen Yuan ◽  
Tanya Tan ◽  
Grace Tan ◽  
Stephen Pandol
Keyword(s):  
Acute Pancreatitis ◽  
Protein Kinase ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Protein Kinase D ◽  
Experimental Acute Pancreatitis

scholarly journals Promiscuous actions of small molecule inhibitors of the protein kinase D-class IIa HDAC axis in striated muscle

FEBS Letters ◽  
2015 ◽  
Vol 589 (10) ◽  
pp. 1080-1088 ◽  
Author(s):  
Douglas D. Lemon ◽  
Brooke C. Harrison ◽  
Todd R. Horn ◽  
Matthew S. Stratton ◽  
Bradley S. Ferguson ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Striated Muscle ◽  
Protein Kinase D

scholarly journals A Novel Small-Molecule Inhibitor of Protein Kinase D Blocks Pancreatic Cancer Growth In vitro and In vivo

2010 ◽  
Vol 9 (5) ◽  
pp. 1136-1146 ◽  
Author(s):  
Kuzhuvelil B. Harikumar ◽  
Ajaikumar B. Kunnumakkara ◽  
Nobuo Ochi ◽  
Zhimin Tong ◽  
Amit Deorukhkar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Protein Kinase ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Cancer Growth ◽  
Protein Kinase D ◽  
Molecule Inhibitor

scholarly journals Novel Small-Molecule Inhibitors of Protein Kinase C Epsilon Reduce Ethanol Consumption in Mice

2018 ◽  
Vol 84 (3) ◽  
pp. 193-201 ◽  
Author(s):  
Angelo Blasio ◽  
Jingyi Wang ◽  
Dan Wang ◽  
Florence P. Varodayan ◽  
Matthew B. Pomrenze ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Ethanol Consumption ◽  
Kinase C ◽  
Protein Kinase C Epsilon

scholarly journals A phenolic small molecule inhibitor of RNase L prevents cell death from ADAR1 deficiency

2020 ◽  
Vol 117 (40) ◽  
pp. 24802-24812 ◽  
Author(s):  
Salima Daou ◽  
Manisha Talukdar ◽  
Jinle Tang ◽  
Beihua Dong ◽  
Shuvojit Banerjee ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Therapeutic Potential ◽  
Protein Kinase Inhibitors ◽  
Response To Treatment ◽  
Rnase L ◽  
Oligoadenylate Synthetase ◽  
In Cells

The oligoadenylate synthetase (OAS)–RNase L system is an IFN-inducible antiviral pathway activated by viral infection. Viral double-stranded (ds) RNA activates OAS isoforms that synthesize the second messenger 2-5A, which binds and activates the pseudokinase-endoribonuclease RNase L. In cells, OAS activation is tamped down by ADAR1, an adenosine deaminase that destabilizes dsRNA. Mutation of ADAR1 is one cause of Aicardi-Goutières syndrome (AGS), an interferonopathy in children. ADAR1 deficiency in human cells can lead to RNase L activation and subsequent cell death. To evaluate RNase L as a possible therapeutic target for AGS, we sought to identify small-molecule inhibitors of RNase L. A 500-compound library of protein kinase inhibitors was screened for modulators of RNase L activity in vitro. We identified ellagic acid (EA) as a hit with 10-fold higher selectivity against RNase L compared with its nearest paralog, IRE1. SAR analysis identified valoneic acid dilactone (VAL) as a superior inhibitor of RNase L, with 100-fold selectivity over IRE1. Mechanism-of-action analysis indicated that EA and VAL do not bind to the pseudokinase domain of RNase L despite acting as ATP competitive inhibitors of the protein kinase CK2. VAL is nontoxic and functional in cells, although with a 1,000-fold decrease in potency, as measured by RNA cleavage activity in response to treatment with dsRNA activator or by rescue of cell lethality resulting from self dsRNA induced by ADAR1 deficiency. These studies lay the foundation for understanding novel modes of regulating RNase L function using small-molecule inhibitors and avenues of therapeutic potential.

SMART Drug Design: Novel Phosphopeptide and ATP Mimetic-Based Small Molecule Inhibitors of the Oncogenic Protein Kinase pp60src (Src)

2005 ◽  
pp. 219-253 ◽  
Author(s):  
T. K. Sawyer ◽  
R. S. Bohacek ◽  
W. C. Shakespeare ◽  
C. A. Metcalf ◽  
Y. Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Drug Design ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Oncogenic Protein ◽  
Smart Drug

scholarly journals Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii

2013 ◽  
Vol 56 (7) ◽  
pp. 3068-3077 ◽  
Author(s):  
Sebastian Lourido ◽  
Chao Zhang ◽  
Michael S. Lopez ◽  
Keliang Tang ◽  
Jennifer Barks ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Toxoplasma Gondii ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Dependent Protein Kinase ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Calcium Dependent Protein Kinase
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