We continue our series in the Biologics campaign – now it is devoted to the Fibroblast growth factor receptor (FGFR).
Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in many developmental and physiological processes including cell growth, survival, differentiation, and angiogenesis. Deregulation of FGFR signaling pathways is frequently implicated in various tumor developments and some other human diseases. There exist various mechanisms to influence oncogenic FGFR signaling such as gene amplification, activating mutations, and chromosomal translocations. Moreover, different inhibitors are also able to block the signaling cascade through direct interaction with FGFRs.
You can find more about FGFR involvement in disorders here.
Earlier approved first-generation pan-FGFR inhibitors displayed high effectiveness but suffer from several drawbacks such as mutation resistance. Here is an example of the discovery and optimization of novel and selective FGFR2/3 inhibitors with nanomolar potency against gatekeeper mutant and wild-type FGFRs. Using scaffold-hopping in core structure guided to reducing the polarity and made cellular permeability better and led to excellent in vitro ADME characteristics and pharmacokinetics in rats.
More information about this research is here.
