{"id":2276,"date":"2020-07-30T09:39:00","date_gmt":"2020-07-30T08:39:00","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?p=2276"},"modified":"2026-01-26T16:28:03","modified_gmt":"2026-01-26T16:28:03","slug":"our-collaborative-work-with-scott-lokeys-lab-at-ucsc","status":"publish","type":"post","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/2020\/07\/30\/our-collaborative-work-with-scott-lokeys-lab-at-ucsc\/","title":{"rendered":"Our collaborative work with Scott Lokey’s Lab at UCSC"},"content":{"rendered":"

Our collaborative work on PROTAC structure-permeability relationships is now published in ACS Med Chem Lett.<\/p>\n

Title<\/strong>: Understanding and Improving the Membrane Permeability of VH032-Based PROTACs<\/p>\n

Authors<\/strong>: Victoria G. Klein, Chad E. Townsend, Andrea Testa, Michael Zengerle, Chiara Maniaci, Scott J. Hughes, Kwok-Ho Chan, Alessio Ciulli, and R. Scott Lokey<\/p>\n

Abstract<\/strong><\/h2>\n

Proteolysis targeting chimeras (PROTACs) are catalytic heterobifunctional molecules that can selectively degrade a protein of interest by recruiting a ubiquitin E3 ligase to the target, leading to its ubiquitylation and degradation by the proteasome. Most degraders lie outside the chemical space associated with most membrane-permeable drugs. Although many PROTACs have been described with potent activity in cells, our understanding of the relationship between structure and permeability in these compounds remains limited. Here, we describe a label-free method for assessing the permeability of several VH032-based PROTACs and their components by combining a parallel artificial membrane permeability assay (PAMPA) and a lipophilic permeability efficiency (LPE) metric. Our results show that the combination of these two cell-free membrane permeability assays provides new insight into PROTAC structure\u2013permeability relationships and offers a conceptual framework for predicting the physicochemical properties of PROTACs in order to better inform the design of more permeable and more effective degraders.<\/p>\n

Congrats to\u00a0Tori Klein<\/a>\u00a0in Scott Lokey\u2019s lab for her work on our PROTAC molecules!\u00a0<\/p>\n