Development of small-molecule therapies for autoimmune diseases

Abstract

Until the recent advent of genetically engineered drugs, small molecules constituted the predominant method of treatment for autoimmune diseases. Both modalities have advantages and disadvantages; while protein-based therapeutics interfere very selectively with the function of their biological targets, they have to be administered subcutaneously or intravenously. Small molecules have the potential for oral administration. Due to their cell permeability, they can interact with extra- and intracellular targets, thus opening opportunities for interfering with novel biochemical pathways. We herein describe the preclinical stages of typical small-molecule research programmes and outline hurdles that may have to be overcome. A few examples of small molecules that are currently under clinical evaluation and arose from diverse discovery pathways will be discussed.

Keywords::

• Hit discovery
• hit-to-lead
• lead optimization

Acknowledgements

The authors would like to thank Wesley Blackaby, Tammy Ladduwahetty, Christopher Newton and Angus MacLeod for helpful discussions.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.