11:30 

Sabrina Yahiya:  Phenotypic characterisation of chemical entities towards antimalarial transmission-blocking drugs of the future

11:45 

Dr Anke Nijhuis:  Targeted protein degradation to treat high grade serous ovarian cancer

12:00   

Main Visiting Speaker – Dr John Harling:   PROTACs: From Chemical Biology Curiosity to New Therapeutic Modality

Abstract

The introduction to the talk will outline some of the work conducted at GSK in collaboration with Craig Crews at Yale which resulted in the development of a new generation of PROTACs which delivered a step change in their degradation efficiency. The man body of the talk will focus on two recent PROTAC drug discovery programs at GSK. RIPK2 is a kinase of the innate immune system implicated in several autoimmune diseases and has a slow re-synthesis rate. The optimisation strategy of a series of RIPK2 PROTACs will be described and their extended in vivo efficacy arising from the PROTAC mechanism of action will be illustrated. The histone acyl transferase, PCAF is known to promote transcription of multiple inflammatory genes. Work on this target will used to illustrate how PROTACs can deliver additional biological activity compared to inhibitors as a result of removal of the protein.

Biography

I conducted both my B.Sc and Ph.D at Imperial College London between 1983-89 under the supervision of Professor William Motherwell. Was the recipient of a SERC/NATO Fellowship to spend two years as a Postdoctoral Researcher in the labs of Professor Phil Magnus at Austin, Texas. Returned to the UK at the end of 1991 to join SmithKlineBeecham as a Medicinal Chemist working on Neuroscience targets. Following the merger with GlaxoWellcome, I moved to the Stevenage site in the newly formed GSK. Here I initially worked on Cardiovascular targets before focussing on Lead Discovery for kinase targets between 2005-7. In 2007 I was appointed as a Medicinal Chemistry Lead Optimisation Department Head in the Respiratory therapeutic area at GSK. In 2012 I became involved in the initiation of an exploratory effort to assess the potential of a new protein degradation technology through collaboration with Professor Craig Crews at Yale. My current position is Senior Scientific Director within Medicinal Chemistry at GSK with a global remit on PROTACs. I also currently hold an Adjunct Professor position within the Chemistry Department at Imperial.