As part of their ongoing effort in
As part of their ongoing effort in the field, Kalypsis recently disclosed that quinazolinones 5 , imidazo[1,2-a] [1,2]diazepin 6  and quinolines 7  all had activity as small molecule modulators of TGR5 (Figure 4). Intercept, however, disclosed different bile GSK1120212 derivatives as TGR5 modulators in recent patent information .
Although TGR5 is the major receptor for bile acids implicated in different disease pathways, other known bile acid receptors, such as farnesoid X receptor (FXR) and pregnane X receptor (PXR), also regulate several metabolic pathways of bile acids 13, 14, 15, 16, 26, 27. The selectivity of different bile acid derivatives for TGR5 over FXR and PXR is not significantly great, though recent evidence suggests that it could be improved through various medicinal chemistry strategies. Producing a potent TGR5 small molecule agonist with high selectivity over a range of other receptors, however, remains the aim of the medicinal chemist.
Conflict of interest