dpp-1

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

DPP-4 GPR119 modulator 1 (Compound 22) is an orally active compound that acts as both a dipeptidyl peptidase IV (DPP-IV) inhibitor and GPR119 agonist, demonstrating a glucose-lowering effect in blood and moderate inhibition of the hERG channel with an IC50 value of 4.9 µM. This compound is applicable in diabetes research [1].

DPP-4-IN-1 (compound d1) is a highly potent inhibitor of DPP-4 (dipeptidyl peptidase 4) with an IC50 of 49 nM, making it suitable for diabetes research [1]. Structurally similar to Alogliptin, it can be effectively utilized for studying diabetes-related mechanisms.

DPP IV hCA II-IN-1 is a potent, selective inhibitor of dipeptidyl peptidase IV (DPP IV) and carbonic anhydrase (CA), exhibiting an IC50 of 0.049 μM for DPP IV and K_i values of 0.0361, 0.0428, 0.0941, 0.1328, 0.2615, and 3.034 μM for CA II, CA VB, CA VA, CA IX, CA I, and CA IV, respectively [1].

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

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.

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.

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.

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

Compound 56 (Antidiabetic agent 2) is a glucose-uptake promoter that inhibits DPP-4, PTP-1B, α-amylase, and α-glucosidase, with IC50 values of 0.036, 0.042, 0.241, and 0.185 μM, respectively. This agent effectively decreases blood glucose levels [1].

DPP, a Platinum(IV) complex with a pterostilbene-derived axial ligand, inhibits the JAK2-STAT3 pathway in breast cancer (BC) cells, demonstrating antiproliferative activity. It activates caspase-3 and cleaved poly ADP-ribose polymerase, inducing apoptosis. Furthermore, DPP enhances the maturation and antigen presentation of dendritic cells and exhibits in vivo safety [1].

ASP8497 is a potent, long-acting DPP-IV inhibitor that improves glucose tolerance by elevating GLP-1 levels in a glucose-dependent insulin-stimulating manner. The compound is used as a therapeutic agent for impaired glucose tolerance and type 2 diabetes.

5,15-Diphenylporphyrin (5,15-DPP) is a selective STAT3-SH2 antagonist with IC50 values of 0.28 μM for STAT3 and 10 μM for STAT1 [1].

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.

Compound 5a, also known as DPP-4 inhibitor 3, is a powerful dipeptidyl peptidase IV (DPP-IV) inhibitor, demonstrating an IC50 value of 0.75 nM. It exhibits outstanding antioxidant and insulinotropic activity [1].

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].

Albiglutide fragment (GLP-1 (7-36) analog) TFA represents a biologically active segment of Albiglutide, resistant to DPP-4 degradation due to its structure as a GLP-1 analog. It functions as a long-acting agonist of the GLP-1 receptor, derived from a fusion of a GLP-1 dimer with the human albumin gene. Clinically, this compound demonstrates a pronounced reduction in glycosylated hemoglobin (A1C) levels, rendering it a valuable therapeutic in type 2 diabetes (T2D) research [1] [2] [3] [4].

O-Benzoyl hydroxylamine exhibits properties as a dipeptidyl peptidase-IV (DPP-IV) inhibitor and demonstrates antidiabetic effects[1].

Fluostatin A, a fluorenone compound initially isolated from Streptomyces, demonstrates selective inhibition towards dipeptidyl peptidase 3 (DPP-3) compared to DPP-1, DPP-2, and DPP-4 with IC50 values of 0.44 µg/ml for DPP-3 and over 100 µg/ml for the others, respectively.

Albiglutide TFA, a glucagon-like peptide (GLP)-1 mimetic, is a long acting GLP-1 receptor agonist. Albiglutide TFA significantly reduces glycosylated hemoglobin (A1C). Albiglutide TFA can be used for type 2 diabetes (T2D) research. Albiglutide TFA is generated by the genetic fusion of a DPP-4-resistant GLP-1 dimer to human albumin [1] [2] [3] .

Begelomab (SAND-26), a murine IgG2b monoclonal antibody targeting DPP-4/CD26, has demonstrated utility in investigating severe refractory idiopathic inflammatory myopathy [1] [2].

Saxagliptin (BMS-477118) is a selective, reversible DPP4 inhibitor with an IC50 of 26 nM.

DPP-IV-IN-5, derived from Lycium barbarum fruits, demonstrates moderate agonistic activity towards peroxisome proliferator-activated receptor (PPARγ), showing EC50 values between 10.09 and 44.26 μM, and exhibits inhibitory activity against dipeptidyl peptidase-4 (DPPIV) with an IC50 of 47.13 μM [1].

Retagliptin (SP2086) hydrochloride serves as a potent inhibitor of dipeptidyl peptidase-4 (DPP-4) and beta-amino acids. This compound aids in the management of type 2 diabetes and enhances glycemic control by extending the activity of intestinal hormones, notably glucagon-like peptide-1 (GLP-1) .

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].

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].

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].

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].

Sitagliptin phenylalanine hydrochloride, a dipeptidyl peptidase-4 (DPP-4) inhibitor [1], is a chemical compound utilized in medical applications.

Teneligliptin hydrobromide hydrate is a potent, competitive, and long-lasting DPP-4 inhibitor, which competitively inhibits human plasma, rat plasma, and human recombinant DPP-4 in vitro, with IC 50 s of approximately 1 nM [1].

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.

H-Pro-Pro-Gln-OH is an oligopeptide exhibiting potent inhibitory activity against dipeptidyl peptidase-IV (DPP-IV) [1].

Kaempferol 3-O-alpha-L-(2, 3-di-Z-p-coumaroyl) rhamnoside (compound 42), a flavonol extracted from Platanus Occidentalis, functions as an inhibitor of alpha-amylase and DPP IV [1].

Fotagliptin benzoate, a Dipeptidyl Peptidase IV (DPP-4) inhibitor with an inhibitory concentration (IC50) of 2.27 nM, demonstrates significant safety in both rat and dog models. It is utilized in Type 2 diabetes mellitus research [1].

Teneligliptin (MP-513) is a potent prolylthiazolidine-based DPP-4 inhibitor that competitively inhibits human plasma, rat plasma, and human recombinant DPP-4 in vitro, with IC50 values of approximately 1 nM.

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.