PMX 900 programme - Base Excision Repair inhibitors

The Base Excision Repair (BER) pathway is one of the most important and ubiquitous of the repair mechanisms employed by cells to repair exogenous and endogenous DNA damage. DNA damage repair (DDR) inhibition has generated increasing interest in recent years as a new approach to anti-cancer therapy, in particular as a result of the success reported in clinical trials with an experimental class of agents known as PARP (Poly(ADP Ribose) Polymerase) inhibitors, which target one of the key proteins in the BER pathway. There is growing evidence to suggest that compounds such as PARP inhibitors that are able to block cellular DNA repair mechanisms can significantly potentiate the effects of traditional cytotoxic drugs such as temozolomide when used in combination with them, as well as acting as monotherapeutic anti-cancer agents in their own right.

The Pharminox team, which has considerable experience in DNA repair, has identified another key, but as yet relatively unexploited, protein in the BER pathway. Based on a detailed study of the scientific literature we believe it represents an important new target for anti-cancer therapy. The Pharminox PMX 900 programme is a rational drug design discovery programme focussed around designing and synthesising specific small molecule inhibitors of this undisclosed target.

This programme is currently in the "hits to leads" phase. The aim is to select a preclinical development candidate within the next 2-3 years to go forward into IND-enabling studies.