Dipeptidyl Peptidase Inhibitor

Sitagliptin (MK-0431) is an orally active and highly selective DPP4 inhibitor with an IC₅₀ value of 19 nM. Sitagliptin blocks the degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) by competing inhibition mechanism (Kᵢ = 1 nM), thereby increasing the level of active incretin. Sitagliptin can also directly stimulate the secretion of GLP-1 by intestinal L cells by activating the cAMP/PKA and ERK1/2 pathways, and this effect is independent of DPP-4. Sitagliptin shows protective effects on pancreatic islet grafts in 1-type diabetes models. Sitagliptin can be used for the study of 1-type and 2-type diabetes.

Talabostat mesylate (Val-boroPro mesylate; PT100 mesylate) is an orally active and nonselective dipeptidyl peptidase IV (DPP-IV) inhibitor (IC₅₀ < 4 nM; K_i = 0.18 nM) and the inhibitor of fibroblast activation protein (FAP) (IC₅₀ = 560 nM), inhibits DPP8/9 (IC₅₀ = 4/11 nM; K_i = 1.5/0.76 nM), quiescent cell proline dipeptidase (QPP) (IC₅₀ = 310 nM), DPP2, and some other DASH family enzymes. Antineoplastic and hematopoiesis- stimulating activities.

Brensocatib (AZD7986) is an oral dipeptidyl peptidase 1 (DPP1) inhibitor with pIC₅₀s of 6.85, 7.6, 7.7, 7.8, and 7.8 in human, mouse, rat, dog and rabbit, respectively.

Linagliptin is a highly potent, selective DPP-4 inhibitor with IC₅₀ of 1 nM.

Puromycin aminonucleoside (NSC 3056) is the aminonucleoside portion of the antibiotic puromycin, and used in nephrosis animal models. Puromycin aminonucleoside induces apoptosis. Puromycin aminonucleoside is a reversible inhibitor of dipeptidyl peptidase II and cytosol alanyl aminopeptidase. Puromycin aminonucleoside induces secretion of cell migrasome.

Val-Pyrrolidide hydrochloride (compound 9) is a DPIV inhibitor. Val-Pyrrolidide hydrochloride can prevent N-terminal truncation of the peptide Gln3-Aβ(1–11)^[1].

AGFAGDDAPR is a bioactive peptide that is a competitive and orally effective inhibitor of dipeptidyl peptidase-IV (DPP-IV). AGFAGDDAPR can enhance the level of GLP-1 in the body by inhibiting DPP-IV, thereby stimulating insulin secretion, improving β-cell function, and inhibiting abnormal proliferation of α-cells, exerting anti-diabetic effects. AGFAGDDAPR can be used for research on type 2 diabetes.

O-Benzoyl hydroxylamine is a DPP-IV inhibitor with anti-diabetic effects (WO2006034435A2).

Diprotin A (Ile-Pro-Ile) is an inhibitor of dipeptidyl peptidase IV (DPP-IV).

Sitagliptin (MK-0431) phosphate is an orally active and highly selective DPP4 inhibitor with an IC₅₀ value of 19 nM. Sitagliptin phosphate blocks the degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) by competing inhibition mechanism (Kᵢ = 1 nM), thereby increasing the level of active incretin. Sitagliptin phosphate can also directly stimulate the secretion of GLP-1 by intestinal L cells by activating the cAMP/PKA and ERK1/2 pathways, and this effect is independent of DPP-4. Sitagliptin phosphate shows protective effects on pancreatic islet grafts in 1-type diabetes models. Sitagliptin phosphate can be used for the study of 1-type and 2-type diabetes.

Vildagliptin (LAF237) is a potent, stable, selective dipeptidyl peptidase IV (DPP-IV) inhibitor with an IC₅₀ of 3.5 nM in human Caco-2 cells. Vildagliptin possesses excellent oral bioavailability and potent antihyperglycemic activity.

Saxagliptin (BMS-477118) is a potent, selective, reversible, competitive and orally active dipeptidyl peptidase-4 (DPP-4) (K_i = 0.6-1.3 nM) inhibitor. Saxagliptin has the peotential for type 2 diabetes mellitus research.

1G244 is a potent DPP8/9 inhibitor with IC₅₀s of 12 nM and 84 nM, respectively. 1G244 does not inhibit DPPIV and DPPII. 1G244 induces apoptosis in multiple myeloma cells and has anti-myeloma effects.

Alogliptin (SYR-322 free base) is a potent, selective and orally active inhibitor of DPP-4 with an IC₅₀ of <10 nM, and exhibits greater than 10,000-fold selectivity over DPP-8 and DPP-9. Alogliptin can be used for the research of type 2 diabetes.

Teneligliptin (MP-513) hydrobromide hydrate is an orally active and selective dipeptidyl peptidase 4 (DPP-4) inhibitor (IC₅₀s: 0.37 and 0.29 nM for the human and rat DPP-4, respectively). Teneligliptin hydrobromide hydrate improves blood glucose levels and can be used in researches related to type 2 diabetes mellitus.

Teneligliptin (MP-513) hydrobromide is an orally active and selective dipeptidyl peptidase 4 (DPP-4) inhibitor (IC₅₀s: 0.37 and 0.29 nM for the human and rat DPP-4, respectively). Teneligliptin hydrobromide improves blood glucose levels and can be used in researches related to type 2 diabetes mellitus.

Omarigliptin (MK-3102) is a potent, selective, orally active and cross the blood-brain barrier dipeptidyl peptidase 4 (DPP-4) inhibitor. Omarigliptin shows anti-parkinsonian activity. Omarigliptin has the neuroprotective effect to improve diabetes-associated cognitive dysfunction.

Trelagliptin (SYR-472) is a potent, orally active and highly selective DPP-4 inhibitor with an IC₅₀ of 4 nM. Trelagliptin succinate improves glycemic control in vivo and can be used for the study of type 2 diabetes mellitus (T2DM).

Sitagliptin (MK-0431) phosphate monohydrate is an orally active and highly selective DPP4 inhibitor with an IC₅₀ value of 19 nM. Sitagliptin phosphate monohydrate blocks the degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) by competing inhibition mechanism (Kᵢ = 1 nM), thereby increasing the level of active incretin. Sitagliptin phosphate monohydrate can also directly stimulate the secretion of GLP-1 by intestinal L cells by activating the cAMP/PKA and ERK1/2 pathways, and this effect is independent of DPP-4. Sitagliptin phosphate monohydrate shows protective effects on pancreatic islet grafts in 1-type diabetes models. Sitagliptin phosphate monohydrate can be used for the study of 1-type and 2-type diabetes.

Nateglinide, a D-phenylalanine derivative, is an orally active and short-acting insulinotropic agent and a DPP IV inhibitor. Nateglinide inhibits ATP-sensitive K⁺ channels in pancreatic β-cells. Nateglinide is used for the treatment of type 2 (non-insulin-dependent) diabetes mellitus.