Wednesday, 13 July 11:00pma – 12:00pm

This seminar will be delivered in Chemistry Lecture Theatre 4 and Online Zoom Please email chemistry.researchsupport@sydney.edu.au for zoom link and password.

Speaker: Dr Madeline Kavanagh; The Scripps Research Institute

Host: Prof. Rich Payne

Title: Chemical proteomics: Driving the discovery of immunomodulatory compounds with unique mechanisms of action

Abstract: Chemical proteomics has emerged over the past decade as a powerful strategy to study biological systems and guide drug design and development. In this presentation, I will outline how activity-based protein profiling coupled with mass spectrometry (ABPP-MS) can be applied to identify novel drug binding sites and guide the development of chemical probes that have unique mechanisms of action. Specifically, I will highlight our recent development of selective inhibitors of the tyrosine kinase JAK1 by targeting an isoform-restricted, allosteric cysteine that was discovered through ABPP-MS. These allosteric JAK1 inhibitors have unprecedented selectivity and a distinct pharmacological profile to existing orthosteric JAK inhibitors, enabling the specific contribution of JAK1 to immune signalling to be studied and reducing the potential for off-target side-effects. Finally, I will overview how we are incorporating functional screening platforms with ABPP-MS target engagement assays to expedite the discovery of ligandable cysteines that modulate protein functions on a proteome wide scale.