dipeptidyl peptidase 1

Brensocatib (AZD7986) is a Dipeptidyl peptidase 1 (DPP1) inhibitor (pIC50s: 6.85, 7.7, 7.6, 7.8, and 7.8 in human, rat, mouse, rabbit, and dog, respectively).

Gly-Pro-pNA hydrochloride (Gly-Pro p-nitroanilide hydrochloride) is a dipeptidyl peptidase inhibitor that inhibits dipeptidyl peptidase II, dipeptidyl peptidase IV and dipeptidyl peptidase IX.

DPP-IV-IN-1 is an effective inhibitor of dipeptidyl peptidase IV (DPP-IV), a serine protease (IC50: 4.6 nM).

Saxagliptin hydrate (Onglyza hydrate) is a selective and reversible DPP4 inhibitor (IC50: 26 nM; Ki: 1.3 nM).

Sitagliptin (MK0431), a new oral hypoglycemic (anti-diabetic drug), is a new dipeptidyl peptidase-4 (DPP-4) inhibitor. This enzyme-inhibiting drug is used either alone or in combination with metformin or thiazolidinedione for treatment of type 2 diabetes mellitus. The drug can competitively inhibit a protein/enzyme and DPP-4, that leads to an incremental amount of active incretins (GLP-1 and GIP), the diminished amount of release of glucagon and increased release of insulin.

Gosogliptin is a potent, orally active, highly selective and competitive inhibitor of DPP-4 (dipeptidyl peptidase 4), increasing the levels of intestinal glucagon peptide (GLP-1) and glucose-dependent proinsulinotropic polypeptide (GIP), thereby enhancing insulin secretion and lowering blood glucose levels. In animal studies, Gosogliptin rapidly, orally and reversibly inhibits plasma DPP-4 activity.

Retagliptin Phosphate (SP 2086) is pharmaceutical composition of DPP-4 inhibitor, for treating type-2 diabetes.

Puromycin aminonucleoside (NSC 3056) is an aminonucleoside antibiotic and a purine analog of puromycin. It can reversibly inhibit dipeptidyl peptidase and cytosolic alanine aminopeptidase, increase podocyte permeability by regulating ZO-1 in an oxidative stress-dependent manner, induce apoptosis, and promote the secretion of migrasomes. It is commonly used to induce nephrotic syndrome models in research.

YH18968, a GPR119 agonist, improves glucose tolerance and enhances blood glucose-lowering effects. When combined with dipeptidyl peptidase-4 (DPP-4) inhibitors, YH18968 increases the plasma levels of active GLP-1 in normal mice.

Cetagliptin is an orally active inhibitor of dipeptidyl peptidase 4 (DPP-4) and CYP2D6, with an IC50 of 6 µM. It acts as a substrate for P-glycoprotein and helps reduce GLP-1 degradation, maintaining postprandial blood glucose levels. It is used in research for type 2 diabetes.

(2S,4R)-Teneligliptin is a selective inhibitor of dipeptidyl peptidase IV (DPP-4). It increases the concentration of active glucagon-like peptide-1 (GLP-1) in plasma, which in turn stimulates insulin secretion when blood glucose levels are elevated, thereby exhibiting hypoglycemic effects. (2S,4R)-Teneligliptin is a promising candidate for research in type 2 diabetes.

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.

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.

DPP-4-IN-16 (Compound 92) is a potent inhibitor of dipeptidyl peptidase-4 (DPP-4) with an IC50 of 0.8 nM. It effectively inhibits the degradation of incretins such as GLP-1 and GIP by DPP-4, thereby enhancing insulin secretion and lowering blood glucose levels. DPP-4-IN-16 holds potential for research into type 2 diabetes.

DPP-1-IN-1 (Compound 14) is an orally active inhibitor of cathepsin C (also known as dipeptidyl peptidase I), with an IC50 of 5.31 nM. It effectively suppresses downstream neutrophil elastase activity in neutrophils mediated by cathepsin C. DPP-1-IN-1 is applicable for studying inflammatory diseases.

DPP9-IN-2 is a selective and potent orally active inhibitor of dipeptidyl peptidase 9 (DPP9), with an IC50 value of 12.9 nM. It exhibits a selectivity index of 59 for DPP8 and shows no significant inhibitory activity on related peptidases, including DPP2, DPP4, FAP, and PREP. DPP9-IN-2 can induce pyroptosis in cancer cells and demonstrates modest synergistic anti-HIV-1 activity when combined with non-nucleoside reverse transcriptase inhibitors. This compound is applicable for research in cancer and infection.

NVP-DPP728 is a potent, reversible, nitrile-dependent inhibitor of dipeptidyl peptidase IV (DPP-IV) with an inhibition constant (K i) of 11 nM for human DPP-IV amidolytic activity. By inhibiting the degradation of glucagon-like peptide-1 (GLP-1), NVP-DPP728 enhances insulin release following glucose intake, making it useful for diabetes research [1].

Omarigliptin is a potent and selective oral dipeptidyl peptidase 4 (DPP4) inhibitor with IC50 value of 1.6 nM. [3]

Neuropeptide Y (NPY) (3-36) is a C-terminal fragment of NPY, a neuropeptide involved in controlling appetite, blood pressure, cardiac contractility, and intestinal secretion. NPY (3-36) is an endogenous peptide produced by cleavage of NPY by dipeptidyl peptidase 4 (DPP-4). It binds selectively to the NPY receptor Y2 (Ki = 0.41 nM in CHP 234 cells) over the Y1 receptor, where it does not bind at concentrations up to 1 μM. NPY (3-36) (0.1 nM) increases migration of human umbilical vein endothelial cells (HUVECs) by 80% after 12 hours in an in vitro wound closure assay. NPY (3-36) corresponds to residues 3-36 of the human and rat protein sequence.

Neuropeptide Y (3-36) (human, rat) is a metabolite of neuropeptide Y (NPY) generated by dipeptidyl peptidase-4 (DPP4) and is known as a selective Y2 receptor agonist, effectively reducing the release of norepinephrine via the Y2 receptor [1][2].

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.

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-4-IN-2 (compound b2) is a structural analog of Alogliptin and a potent dipeptidyl peptidase 4 (DPP-4) inhibitor with an IC50 value of 79 nM [1], suitable for diabetes research.

Vildagliptin dihydrate (LAF237 dihydrate) is a potent and stable dipeptidyl peptidase IV (DPP-IV) inhibitor with an IC50 of 3.5 nM in human Caco-2 cells, exhibiting exceptional oral bioavailability and significant antihyperglycemic activity [1].