dpp9

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

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.

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

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.

DBPR108 is an orally bioavailable dipeptide-derived DPP4 inhibitor (IC50: 15 nM) and it has no inhibition on DDP8 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.

Sulphostin is a covalent inhibitor of dipeptidyl peptidase 4 (DPP4), dipeptidyl peptidase 9 (DPP9), and dipeptidyl peptidase 8 (DPP8), with IC50 values of 79, 1392, and 6930 nM, respectively. It induces phosphorylation of amino sulfamide esters, irreversibly inhibiting enzyme activity. Sulphostin is applicable in inflammation and cancer research.

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.

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).

ICeD-2, an inducer of cell death, effectively induces the killing of HIV-1 infected cells, a process reliant on HIV-1 protease activity. It significantly inhibits the hydrolysis of Gly-Pro-AMC by dipeptidyl peptidases DPP8 and DPP9, and robustly stabilizes DPP9 in peripheral blood mononuclear cells (PBMCs) [1].

NH2-UAMC1110 TFA is a derivative of UAMC1110 bearing an aminobutoxy group for the synthesis of FAPI-QS. UAMC1110 is a novel selective fibroblast-activated protein (fap) inhibitor exhibiting low nanomolar inhibition of the related dipeptidyl peptidases (dpps), dppiv, dpp9, dppii, and (prep). dppiv, dpp9, dppii, and (prep).