dpp-9

Anagliptin (SK-0403) is a potent inhibitor of DPP-4 (IC50 of 3.8 nM) used in the treatment of type 2 diabetes mellitus.

DPP-4-IN-9 (compound 6l) is a potent dipeptidyl peptidase DPP-4 inhibitor, exhibiting an IC50 of 8.22 nM. Additionally, this compound demonstrates antihyperglycemic activity [1].

Alogliptin Benzoate (SYR 322)(SYR 322), an effective and specific DPP-4 inhibitor (IC50<10 nM), exhibits greater than 10, 000-fold selectivity over DPP-8 9. Alogliptin may inhibit inflammatory responses by preventing the toll-like receptor 4 (TLR-4)-mediated formation of proinflammatory cytokines.

Alogliptin (SYR-322)(SYR-322) is a potent, selective inhibitor of DPP-4 with IC50 of <10 nM, exhibits greater than 10, 000-fold selectivity over DPP-8 and DPP-9.

Teneligliptin hydrobromide (MP-513 (hydrobromide)) is a novel, potent, and long-lasting dipeptidyl peptidase-4 inhibitor; competitively inhibited human plasma, rat plasma, and human recombinant DPP-4 in vitro, with IC50 values of approximately 1 nM.

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase 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 dipeptidyl peptidase (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 dipeptidyl peptidase 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 dipeptidyl peptidase 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.

DPP-IV-IN-2 (H-Lys(4-nitro-Z)-pyrrolidide) is an inhibitor of both DP8 9 and dipeptidyl peptidase IV (IC50s: 0.1 and 0.95 μM).

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 dipeptidyl peptidase 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.

Anagliptin (SK-0403) hydrochloride is a potent, highly selective, orally active inhibitor of dipeptidyl peptidase 4 (DPP-4) (IC50: 3.8 nM), with relatively weak selectivity for DPP-8 (IC50: 68 nM) and DPP-9 (IC50: 60 nM).

Gemigliptin Tartrate (LC15-0444 tartrate) is a highly selective, reversible and competitive inhibitor of dipeptidyl peptidase-4 (DPP-4). It has an IC50 of 10.3 nM for human recombinant DPP-4. Gemigliptin tartrate exhibits potent anti-glycation properties.

GLP-1(9-36)amide TFA, a predominant metabolite of glucagon-like peptide-1-(7-36)amide synthesized through dipeptidyl peptidase-4 (DPP-4) activity, functions as an antagonist to the human pancreatic GLP-1 receptor [1] [2].