Lecture 'Tackling protein-protein interactions (PPIs) through stabilisation of desired conformations of target proteins. The Discovery of Small molecule Inhibitors of TNF'

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Students, Employees, Alumni, Business
28-04-2020 from 14:00 to 15:00
UGent-VIB-onderzoeksgebouw, Technologiepark 71, 9052 Zwijnaarde
VIB-UGent Center for Inflammation Research (WE14, WE10, WE02, GE35)
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The discovery of orally available small molecule inhibitors of tumor necrosis factor (TNF) will be discussed by James O'Connell (UCB Pharma).

James O'Connell (UCB Pharma, Slough, UK) is our guest speaker. More information on his talk:

Despite the clinical benefit demonstrated by TNF inhibition, to date no small molecule inhibitor of TNF has entered clinical development. Small molecule inhibitors of TNF have therefore, long been considered one of the holy grails of drug discovery. Many proteins are dynamic and switch between signalling and non-signalling conformations. Here we report how fragments were used to discover orally available small molecule inhibitors of TNF that stabilise a non-signalling conformer of the protein. These compounds may provide oral alternatives to the biologics in diseases like rheumatoid arthritis and may also lead to new therapies for diseases where tissue access limits biologics.
We believe that stabilisation of inactive conformers may prove to be a general method of drugging proteins using traditional medicinal chemistry.