Talabostat (Val-boroPro, PT-100) is a dipeptidyl peptidase inhibitor with IC50 values of <4 nM, 4 nM, 11 nM, 310 nM, 560 nM and 390 nM for DPP-IV, DPP8, DPP9, QPP, FAP and PEP respectively. It has antineoplastic and hematopoiesis- stimulating activities.
In vitro, talabostat upregulates cytokines/chemokines in human bone marrow stromal cells[2]. Talabostat (Val-boroPro) induces monocytes and macrophage cell death. Val-boroPro induced pyroptosis requires caspase-1[4].
Talabostat has been shown to produce potent antitumor effects when administered orally in multiple mouse tumor models. Val-boroPro mediates complete tumor regression via a novel mechanism that requires more rapid DC trafficking and subsequent acceleration of T cell priming[3]. In tumor stroma, talabostat can directly target FAP expressed by reactive fibroblasts. Talabostat stimulates innate and adaptive immune responses against tumors involving transcriptional upregulation of cytokines and chemokines[2]. Val-boroPro is known to stimulate the transcriptional upregulation several cytokines, including IL-1β, IL-6, G-CSF, and CXCL1/KC, in both tumors and tumor-draining lymph nodes, and to increase the mouse serum protein levels of several of these cytokines, including G-CSF and CXCL1/KC[4].
[1] Lankas GR, et al. Diabetes. 2005, 54(10):2988-94. [2] Michael Jesson, et al. American Association for Cancer Research. 2007, 67(9):Supplement. [3] Walsh MP, et al. PLoS One. 2013, 8(3):e58860.