dpp-8

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.

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

1G244 is an inhibitor of DPP8/9 with antiatherosclerotic and antimyeloma properties. 1G244 had the IC50 values of 14 and 53 nM against DPP8 and DPP9, and The Ki values for 1G244 were 0.9 and 4.2 nM for DPP8 and DPP9

DPP8/9-IN-1 (Compound 16) is a selective covalent inhibitor of dipeptidyl peptidase 8 and 9 (DPP8/9), with IC50 values of 14 nM and 298 nM, respectively. It irreversibly binds to the active site serine (such as S730 in DPP9) through a phosphate ester warhead, blocking substrate binding and inhibiting DPP8/9-mediated protein processing. DPP8/9-IN-1 holds potential for research in cancer and inflammatory diseases.

DPP8/9-IN-2 (Compound 21) is an inhibitor targeting DPP8 and DPP9 with IC50 values of 0.22 nM and 3 nM, and Ki values of 2.9 nM and 6 nM, respectively. It exhibits certain cardiac toxicity, with IC50 values against the hERG potassium channel, Nav1.5 sodium channel, and Cav1.2 calcium channel of 0.7 μM, 29.0 μM, and 27.7 μM. DPP8/9-IN-2 is applicable for research into diseases such as cancer.

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).

DPP9-IN-1 (Compound 42) is an inhibitor of dipeptidyl peptidase 9 (DPP9), with an IC50 of 3 nM for DPP9 and an IC50 of 0.6 μM for DPP8. In THP-1 cells, DPP9-IN-1 induces LDH release in a concentration-dependent manner.

NZ-97 is an inhibitor of dipeptidyl peptidase 4 (DPP4) with an IC50 of 18 nM. It exhibits low initial plasma exposure with a Cmax of 0.13 µM and is eliminated within 8 hours. NZ-97 can ameliorate lipopolysaccharides-induced lung injury and bleomycin-induced pulmonary fibrosis in mouse models.

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.

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.

DPP-4-IN-8 (compound 27) is a potent and selective inhibitor of dipeptidyl peptidase 4 (DPP4), with an inhibition constant (Ki) of 0.96 μM. It inhibits the dipeptidase activity of DPP4 in both Caco-2 and HepG-2 cells and dose-dependently reduces the expression of chemokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) [1].

Alogliptin (Standard) is a reference standard for research and analysis in studies involving Alogliptin. 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.