dipeptidyl

Dipeptidyl peptidase-IV (DPP-IV) is an enzyme that deactivates incretin hormones such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are crucial in regulating blood glucose levels. Additionally, DPP-IV functions as a binding protein and ligand for various extracellular molecules. This enzyme is instrumental in research related to diabetes and cancer.

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

P32 98 hemifumarate is a dipeptidyl peptidase IV (DPP4) inhibitor with hypoglycemic properties that improves insulin sensitivity and β-cell responsiveness in the Zucker diabetic rat model, and may be useful in studies of type 2 diabetes and colitis.

Cameglipti, a dipeptidyl peptidase IV (DPP-4) inhibitor, is used potentially for the treatment of type 2 diabetes.

Imigliptin (KBP 3853) is a novel dipeptidyl peptidase-4 inhibitor for the study of type 2 diabetes.

TS-021 is a selective dipeptidyl peptidase 4 (DPP-4) inhibitor with antidiabetic activity for the study of type 2 diabetes.

Leukotriene E4 (LTE4) (LTE4) is produced by the action of dipeptidyl peptidase on LTD4 and is a component of the Slow Reactive Substance of Anaphylaxis (SRS-A).LTE4 is present in plasma and urine and can be used to detect asthma.

Denagliptin is a small molecule dipeptidyl peptidase IV (DPP-4) inhibitor for the treatment of endocrine Ü metabolic diseases and can be used in the study of type 2 diabetes.

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

Linagliptin (BI 1356) is a potent, orally bioavailable dihydropurinedione-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity.

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.

Sitagliptin phosphate monohydrate (MK-0431 phosphate monohydrate) is a potent DPP-IV inhibitor with an IC50 of 19 nM in Caco-2 cell extracts.

Vildagliptin (LAF237) is a cyanopyrrolidine-based, orally bioavailable inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Vildagliptin's cyano moiety undergoes hydrolysis and this inactive metabolite is excreted mainly via the urine.

Nateglinide (Senaglinide) is an oral hypoglycemic agent and amino acid derivative that stimulates insulin secretion from the pancreas and is used in the therapy of type 2 diabetes. Nateglinide has been linked to rare instances of clinically apparent acute liver injury.

Trelagliptin succinate (SYR-472 succinate) is a long-acting inhibitor of dipeptidyl peptidase-4 (DPP-4), being developed for the treatment of type 2 diabetes (T2D).

Sitagliptin phosphate (MK-0431 phosphate) is a dipeptidyl peptidase-4 (DPP4) inhibitor.

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.

Trelagliptin (SYR-472) is a highly specific, long-acting DPP-4 inhibitor.

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.

MK-0626 is an orally available dipeptidyl peptidase IV (DPP-4) inhibitor that attenuates hepatic steatosis and accumulation by enhancing AMPK activity.MK-0626 attenuates TAC-induced diabetic pancreatic islet injury by restoring the expression of GLP-1R.MK-0626 is able to increase circulating endothelial progenitor cell numbers and endothelial-type nitric oxide synthase expression by promoting neoangiogenesis.

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

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.

Talabostat mesylate (PT100) is an orally active, selective inhibitor of dipeptidyl peptidases IV (DPP4, IC50: 0.18 nM), including tumor-associated fibroblast activation protein. This agent may also stimulate the production of colony stimulating factors, such as granulocyte colony-stimulating factor (G-CSF), resulting in the stimulation of hematopoiesis.