Abstract 2740: Antitumor activity of BMS-754807, a small molecule inhibitor of insulin-like growth factor-1 receptor / insulin receptor, in combination with gemcitabine in pancreatic cancer

2012 ◽  
Author(s):  
Niranjan Awasthi ◽  
Changhua Zhang ◽  
Margaret A. Schwarz ◽  
Roderich E. Schwarz
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factor ◽  
Antitumor Activity ◽  
Insulin Receptor ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Insulin Like Growth Factor ◽  
Molecule Inhibitor

scholarly journals BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR

2009 ◽  
Vol 8 (12) ◽  
pp. 3341-3349 ◽  
Author(s):  
Joan M. Carboni ◽  
Mark Wittman ◽  
Zheng Yang ◽  
Francis Lee ◽  
Ann Greer ◽  
...  
Keyword(s):  
Growth Factor ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Insulin Like Growth Factor ◽  
Molecule Inhibitor

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 A Novel Chemical Attack on Notch-mediated transcription by targeting the NACK ATPase

2021 ◽  
Author(s):  
G. Diluvio ◽  
T. T. Kelley ◽  
M. Lahiry ◽  
A. Alvarez Trotta ◽  
E. M. Kolb ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Mouse Models ◽  
Small Molecule ◽  
Ternary Complex ◽  
Small Molecule Inhibitor ◽  
Chemical Attack ◽  
Dependent Function ◽  
Molecule Inhibitor ◽  
Efficacious Treatment ◽  
Notch Activation

Abstract Notch Activation Complex Kinase, NACK, is a component of the Notch transcriptional machinery critical to Notch-mediated tumorigenesis. However, the mechanism by which NACK regulates the Notch-mediated transcription is not well understood. Here we demonstrate that NACK binds and hydrolyses ATP and that only ATP-bound NACK is able to bind to the Notch Ternary Complex (NTC). Considering this we sought to identify inhibitors of this ATP-Dependent function and, using computational pipelines, discovered the first small molecule inhibitor of NACK, Z271-0326, that directly blocks the activity of Notch-mediated transcription and shows potent antitumor activity in PDX mouse models. In conclusion, we have discovered the first inhibitor that holds promise for efficacious treatment of Notch-driven cancers by blocking the Notch downstream NTC activity.

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