Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidylpeptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM. Talabostat is a nonselective DPP-IV inhibitor, inhibiting DPP8/9, FAP, DPP2 and some other DASH family enzymes essentially as potently as it inhibits DPP-IV[1]. Talabostat stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. The inhibition of two serine proteases, DPP8 and DPP9, activates the proprotein form of caspase-1 independent of the inflammasome adaptor ASC[2]. Talabostat competitively inhibits the dipeptidylpeptidase (DPP) activity of FAP and CD26/DPP-IV, and there is a high-affinity interaction with the catalytic site due to the formation of a complex between Ser630/624 and the boron of talabostat[3]. Talabostat can stimulate immune responses against tumors involving both the innate and adaptive branches of the immune system. In WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, PT-100 causes regression and rejection of tumors. The antitumor effect appears to involve tumor-specific CTL and protective immunological memory. Talabostat treatment of WEHI 164-inoculated mice increases mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells[3]. Talabostat treated mice show significant less fibrosis and FAP expression is reduced. Upon PT100 treatment, significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs are also observed. Treatment with PT100 in this murine model of pulmonary fibrosis has an anti-fibro-proliferative effect and increases macrophage activation[4]. [1]. Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidylpeptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. [2]. Okondo MC, et al. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. [3]. Adams S, et al. PT-100, a small molecule dipeptidylpeptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. [4]. Egger C, et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72.
DPPI 1c hydrochloride is an inhibitor of dipeptidylpeptidase IV (IC50 = 104 nM) that shows selectivity over enzymes with DPP-like activity (IC50 > 30 μM).
Saxagliptin is a new oral hypoglycemic of the new dipeptidylpeptidase-4 (DPP-4) inhibitor class of drugs. Saxagliptin is a competitive DPP4 inhibitor that slows the inactivation of the incretin hormones and reducing fasting and postprandial glucose conce
Dutogliptin (PHX-1149 free base) is an oral, effective and selective dipeptide-peptide-4 (DPP4) inhibitor for the treatment of type 2 diabetes mellitus.
Evogliptin(DA-1229) is a potent and selective DPP4 inhibitor (dipeptidylpeptidase 4 inhibitor) that can improve insulin resistance and delays the onset of diabetes. Evogliptin delays the onset of diabetes in young db/db mice and improves insulin sensitiv
Aminopeptidase N (AP-N) inhibitor is a reversible inhibitor of AP-N/CD13 (IC50 = 25 μM). It is selective for AP-N/CD13 over matrix metalloproteinase-9 (MMP-9), angiotensin converting enzyme (ACE), neutral endopeptidase (NEP), γ-glutamyl transpeptidase, and the serine proteases dipeptidylpeptidase 4 (DPP-4) and cathepsin G at a concentration of 1 mM. AP-N inhibitor is non-cytotoxic to U937 cells at a concentration of 100 μM.