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22 February 2017
Time: 16:00 to 17:00
Location: Lecture Theatre D

Mighty oaks from little acorns grow? - Targeting Protein-Protein Interactions in Oncology with Fragment Based Drug Discovery

Martin Drysdale, CR-UK Beatson Institute, Drug Discovery Unit


The use of weak binding "fragments" of molecules is now recognised as an efficient and robust method of hit identification in the drug discovery process. The use and integration off fragment hits into successful lead optimisation is the critical determinant of whether this technology will become accepted as a significant tool in drug discovery. A number of compounds which have evolved using fragment based hit identification are now in phase I-III clinical trials. The first registered drug which utilized Fragment Based Lead Identification, Vemurafinib to treat B-Raf mutant melanoma, is now in the clinic and recently the FDA approved Venclexta (venetoclax – ABT-199) for the treatment of patients with chronic lymphocytic leukemia (CLL) who have a chromosomal abnormality called 17p deletion, as the second. This is a technology which has found a permanent place in the armory of the Drug Discovery Scientist.

In the Drug Discovery Programme at the Cancer Research UK Beatson Institute we are exploiting the basic biology strengths within the Institute and wider Cancer Research UK network, to investigate some of the most exciting and challenging cancer targets. This includes targeting mechanisms important in invasion and metastasis as well as highly validated but challenging protein-protein interaction (PPI) targets. I will describe our forays in this area which involve fragment based methods of hit identification coupled with structure based compound evolution.