Therapeutic Potential of Allosteric Modulation of FGF Receptors

Fibroblast Growth Factor receptors (FGFR) function as receptor tyrosine kinases (RTKs) and represent major targets for drug development. Traditional RTK inhibitors block orthosteric binding of ligands and substrates. Allosteric ligands provide a rich source of possible drug targets with clear therapeutic advantages, but the complexity of their mechanisms makes the discovery and development of allosteric drugs challenging. The FGFR has recently been targeted by SSR128129E (SSR), an extracellularly acting small-molecule allosteric modulator. In this chapter, we discuss the mode-of-action of SSR and the advantages and challenges associated with allosteric targeting of FGFRs. The allosteric targeting of the FGFR by SSR has also shown therapeutic potential for the treatment of cancer and inflammatory diseases and represents a novel research tool to unravel the biology of RTK function.