Talabostat . mesylate

Talabostat is an orally bioavailable non-selective inhibitor of dipeptidyl-peptidases (DPPs), including DPP-4, DPP-7/QPP, DPP-8, DPP-9, fibroblast activation protein (FAP) and prolyl endopeptidase (PREP, PEP) (IC50s = >4, 310, 4, 11, 560 and 390 nM, respectively). Talabostat induces powerful anti-tumor immune responses in cancer models. Talabostat is a NLRP1 and caspase recruitment domain family member 8 (CARD8) inflammasome activator. Talabostat triggers an immunostimulatory form of programmed cell death known as pyroptosis selectively in monocytes and macrophages. DPP8/9 inhibition by Talabostat activates the inflammasome sensor protein Nlrp1b, which in turn activates pro-caspase-1 to mediate pyroptosis, suggesting that DPP8/9 serve as an intracellular checkpoint to restrain Nlrp1b and the innate immune system. Talabostat has anti-obesity properties and lowers body weight, blood glucose, plasma insulin and total cholesterol while improving glucose tolerance and insulin sensitivity in mouse models. It has also been shown to elevate FGF21 levels in plasma.