David Whomble
6 Papers
1 Citations
David Whomble is an academic researcher. The author has contributed to research in topics: Chemistry & Muscarinic acetylcholine receptor. The author has an hindex of 1, co-authored 2 publications.
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Papers
Development of VU6019650: A Potent, Highly Selective, and Systemically Active Orthosteric Antagonist of the M5 Muscarinic Acetylcholine Receptor for the Treatment of Opioid Use Disorder.
Aaron T. Garrison,Douglas L. Orsi,Rory A. Capstick,David Whomble,Jin-ming Li,Trever R. Carter,Andrew S. Felts,Paige N. Vinson,Allie Han,Krishma Hajari,Hyekyung P. Cho,Laura B. Teal,Madeline G. Ragland,Masoud Ghamari-Langroudi,Michael Bubser,Si-Jia Chang,Nathalie Schnetz-Boutaud,Olivier Boutaud,Anna L. Blobaum,Daniel J. Foster,Colleen M. Niswender,P. Jeffrey Conn,Craig W. Lindsley,Carrie K. Jones,Changho Han +24 more
TL;DR: In acute brain slice electrophysiology studies, VU6019650 (27b) blocked the nonselective muscarinic agonist oxotremorine-M-induced increases in neuronal firing rates of midbrain dopamine neurons in the ventral tegmental area, a part of the mesolimbic dopaminergic reward circuitry.
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Discovery of a potent M5 antagonist with improved clearance profile. Part 1: piperidine amide-based antagonists.
Rory A. Capstick,David Whomble,Douglas L. Orsi,Andrew S. Felts,Paige N. Vinson,Si-Jia Chang,Anna L. Blobaum,Colleen M. Niswender,P. Jeffrey Conn,Carrie K. Jones,Craig W. Lindsley,Changho Han +11 more
TL;DR: In this paper , a mix and match approach between VU6019650 (lead) and VU0500325 (HTS hit) generated a piperidine amide-based novel M5 antagonist series.
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Discovery of VU6083859, a TAOK1 Selective Inhibitor, and VU6080195, a pan-TAOK Activator.
Daniel C Schultz,Lauren C. Parr,Hunter Sweet,Sean Lamb,Julie L. Engers,Nathaniel C Napier,Hallie G McKinnie,David Whomble,Valerie M Kramlinger,Olivier Boutaud,Craig W. Lindsley +10 more
TL;DR: Researchers discovered VU6083859, a selective TAOK1 inhibitor, and VU6080195, a pan-TAOK activator, with potential therapeutic applications in breast cancer, neurodegeneration, and neurodevelopmental disorders, providing a foundation for further optimization and validation of TAO kinase modulation in the CNS.
Discovery of 7-(Pyridin-3-yl)thieno[3,2-b]pyridine-5-carboxamides as Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5.
S. H. Henderson,Anna E Ringuette,David Whomble,Rory A. Capstick,Alexa E Richardson,Mallory A Maurer,Natasha B Billard,Joshua C Wilkinson,Sri H Kethanapalli,Colleen M. Niswender,Jerri M. Rook,Anna L. Blobaum,Olivier Boutaud,Andrew S. Felts,P. J. Conn,Craig W. Lindsley,Kayla J Temple +16 more
Abstract: Herein, we report the structure-activity relationship (SAR) to develop novel mGlu5 negative allosteric modulator (NAM) scaffolds devoid of the aryl/heterobiaryl acetylene moiety found in many historic mGlu5 NAMs, which has been linked to metabolic liabilities and hepatotoxicity. This endeavor utilized a scaffold-hopping strategy from the predecessor compound VU6031545, in which we replace an ether-linked tetrahydrofuran with various carbon-linked heteroaryl motifs to generate highly potent and selective mGlu5 NAMs. One such compound, VU6035386, displayed low nanomolar potency against human mGlu5 and was highly brain penetrant. Moreover, VU6035386 showed a vast improvement in predicted human hepatic clearance versus predecessor compound VU6031545.
Discovery of Thieno[3,2-b]pyridine-5-carboxamide and 2,3-Difluorobenzamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5
Katherine E. Crocker,S. H. Henderson,Rory A. Capstick,David Whomble,Aaron M. Bender,Andrew S. Felts,Changho Han,Julie L. Engers,Natasha Billard,Mallory A Maurer,Hyekyung P. Cho,Alice L. Rodriguez,Colleen M. Niswender,Jordan C. O’Neill,Katherine J. Watson,Si-Jia Chang,Anna L. Blobaum,Olivier Boutaud,Weimin Peng,Jerri M. Rook,P. J. Conn,Craig W. Lindsley,Kayla J. Temple +22 more