scholarly journals A Nanomolar-Potency Small Molecule Inhibitor of Regulator of G-Protein Signaling Proteins

Biochemistry ◽  
2011 ◽  
Vol 50 (15) ◽  
pp. 3181-3192 ◽  
Author(s):  
Levi L. Blazer ◽  
Haoming Zhang ◽  
Emma M. Casey ◽  
Stephen M. Husbands ◽  
Richard R. Neubig
Keyword(s):  
G Protein ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
G Protein Signaling ◽  
Signaling Proteins ◽  
Protein Signaling ◽  
Molecule Inhibitor

scholarly journals Reversible, Allosteric Small-Molecule Inhibitors of Regulator of G Protein Signaling Proteins

2010 ◽  
Vol 78 (3) ◽  
pp. 524-533 ◽  
Author(s):  
Levi L. Blazer ◽  
David L. Roman ◽  
Alfred Chung ◽  
Martha J. Larsen ◽  
Benjamin M. Greedy ◽  
...  
Keyword(s):  
G Protein ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
G Protein Signaling ◽  
Signaling Proteins ◽  
Protein Signaling

scholarly journals Interplay of cysteine exposure and global protein dynamics in small-molecule recognition by a regulator of G-protein signaling protein

2018 ◽  
Vol 87 (2) ◽  
pp. 146-156 ◽  
Author(s):  
Mohammadjavad Mohammadi ◽  
Hossein Mohammadiarani ◽  
Vincent S. Shaw ◽  
Richard R. Neubig ◽  
Harish Vashisth
Keyword(s):  
Protein Dynamics ◽  
G Protein ◽  
Small Molecule ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Signaling Protein ◽  
Molecule Recognition

scholarly journals Genetic Analysis of Rare Human Variants of Regulators of G Protein Signaling Proteins and Their Role in Human Physiology and Disease

2018 ◽  
Vol 70 (3) ◽  
pp. 446-474 ◽  
Author(s):  
Katherine E. Squires ◽  
Carolina Montañez-Miranda ◽  
Rushika R. Pandya ◽  
Matthew P. Torres ◽  
John R. Hepler
Keyword(s):  
Human Physiology ◽  
Genetic Analysis ◽  
G Protein ◽  
G Protein Signaling ◽  
Signaling Proteins ◽  
Protein Signaling

scholarly journals Screen Targeting Lung and Prostate Cancer Oncogene Identifies Novel Inhibitors of RGS17 and Problematic Chemical Substructures

2018 ◽  
Vol 23 (4) ◽  
pp. 363-374 ◽  
Author(s):  
Christopher R. Bodle ◽  
Josephine H. Schamp ◽  
Joseph B. O’Brien ◽  
Michael P. Hayes ◽  
Meng Wu ◽  
...  
Keyword(s):  
G Protein ◽  
Small Molecule ◽  
High Throughput Screening ◽  
Biochemical Characterization ◽  
Parent Compound ◽  
Receptor Activation ◽  
G Protein Signaling ◽  
Conservation Of Resources ◽  
Protein Signaling ◽  
Rgs Protein

Regulator of G protein signaling (RGS) proteins temporally regulate heterotrimeric G protein signaling cascades elicited by G protein–coupled receptor activation and thus are essential for cell homeostasis. The dysregulation of RGS protein expression has been linked to several pathologies, spurring discovery efforts to identify small-molecule inhibitors of these proteins. Presented here are the results of a high-throughput screening (HTS) campaign targeting RGS17, an RGS protein reported to be inappropriately upregulated in several cancers. A screen of over 60,000 small molecules led to the identification of five hit compounds that inhibit the RGS17-Gαo protein-protein interaction. Chemical and biochemical characterization demonstrated that three of these hits inhibited the interaction through the decomposition of parent compound into reactive products under normal chemical library storage/usage conditions. Compound substructures susceptible to decomposition are reported and the decomposition process characterized, adding to the armamentarium of tools available to the screening field, allowing for the conservation of resources in follow-up efforts and more efficient identification of potentially decomposed compounds. Finally, analogues of one hit compound were tested, and the results establish the first ever structure-activity relationship (SAR) profile for a small-molecule inhibitor of RGS17.

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