Correction to Small Molecule Disruptors of the Glucokinase–Glucokinase Regulatory Protein Interaction: 1. Discovery of a Novel Tool Compound for in Vivo Proof-of-Concept

2014 ◽  
Vol 57 (6) ◽  
pp. 2820-2820
Author(s):  
Kate S. Ashton ◽  
Kristin L. Andrews ◽  
Marian C. Bryan ◽  
Jie Chen ◽  
Kui Chen ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Interaction ◽  
Regulatory Protein ◽  
Proof Of Concept ◽  
Glucokinase Regulatory Protein

Small Molecule Disruptors of the Glucokinase–Glucokinase Regulatory Protein Interaction: 4. Exploration of a Novel Binding Pocket

2014 ◽  
Vol 57 (14) ◽  
pp. 5949-5964 ◽  
Author(s):  
Fang-Tsao Hong ◽  
Mark H. Norman ◽  
Kate S. Ashton ◽  
Michael D. Bartberger ◽  
Jie Chen ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Interaction ◽  
Regulatory Protein ◽  
Binding Pocket ◽  
Glucokinase Regulatory Protein

P4-164: Aβ oligomers as tractable drug targets in Alzheimer's disease: in vivo proof of concept for the oligomer-binding small-molecule therapeutic candidate cbb68

2015 ◽  
Vol 11 (7S_Part_18) ◽  
pp. P841-P842
Author(s):  
Armand W.J.W. Tepper ◽  
Elizabeth C. de Boer ◽  
Emily Hoogveld ◽  
Joost D.J. Vis ◽  
Ivar C. Schut ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecule ◽  
Drug Targets ◽  
Proof Of Concept ◽  
Aβ Oligomers

scholarly journals Small-molecule inhibitor targeting the Hsp90-Cdc37 protein-protein interaction in colorectal cancer

2019 ◽  
Vol 5 (9) ◽  
pp. eaax2277 ◽  
Author(s):  
Lei Wang ◽  
Lixiao Zhang ◽  
Li Li ◽  
Jingsheng Jiang ◽  
Zhen Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Small Molecule ◽  
Protein Interaction ◽  
Small Molecule Inhibitor ◽  
Protein Protein Interaction ◽  
Molecule Inhibitor ◽  
Dependent Cell ◽  
Hsp90 Chaperone

Disrupting the interactions between Hsp90 and Cdc37 is emerging as an alternative and specific way to regulate the Hsp90 chaperone cycle in a manner not involving adenosine triphosphatase inhibition. Here, we identified DDO-5936 as a small-molecule inhibitor of the Hsp90-Cdc37 protein-protein interaction (PPI) in colorectal cancer. DDO-5936 disrupted the Hsp90-Cdc37 PPI both in vitro and in vivo via binding to a previously unknown site on Hsp90 involving Glu47, one of the binding determinants for the Hsp90-Cdc37 PPI, leading to selective down-regulation of Hsp90 kinase clients in HCT116 cells. In addition, inhibition of Hsp90-Cdc37 complex formation by DDO-5936 resulted in a remarkable cyclin-dependent kinase 4 decrease and consequent inhibition of cell proliferation through Cdc37-dependent cell cycle arrest. Together, our results demonstrated DDO-5936 as an identified specific small-molecule inhibitor of the Hsp90-Cdc37 PPI that could be used to comprehensively investigate alternative approaches targeting Hsp90 chaperone cycles for cancer therapy.

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