Medicinal Chemistry

The application of medicinal chemistry to discover small molecules to control cell fate has attracted immense interest in recent years. The ability to control each step in the proliferation and differentiation, but also dedifferentiation/ reprogramming processes would allow control of the selective production of different tissue types both in vitro and, importantly in many instances, directly in vivo. The use of chemicals to control cell fate decisions can offer unprecedented advantages over other techniques in terms of speed, cost, reproducibility and the ability to influence cell fate reversibly.

One of the potentially most powerful applications of using small molecules to direct cell fate would be the ability to manipulate these cells in vivo. There would be enormous advantages with the capability to safely proliferate and specify the fate of a patient's own endogenous stem or progenitor cells solely through administering a drug, thereby precluding the need for cell therapies. There is a growing body of evidence to support the presence of resident adult stem cells in many tissues of the body that retain the ability to proliferate, differentiate, migrate and can replenish or repair damage to the parent tissue. Recent years have seen the launch of the first small molecule drugs deliberately designed to target such mechanisms, Eltrombopag and Plerixafor, and several more agents have recently entered clinical trials or are in preclinical development.

In Oxford through multidisciplinary collaborative networks within OSCI, we are actively engaged in discovering new small molecules and new mechanisms to enable the manipulation of cell fate both in vitro and in vivo in a range of tissue types.