DPP-4 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.

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

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.

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.

γ-Glu-Tyr is an orally active gut microbiota-derived metabolite and a competitive DPP-IV inhibitor with an IC₅₀ of 6.77 mM against hDPP-IV. γ-Glu-Tyr weakly activates hCaSR. γ-Glu-Tyr decreases colonic pro-inflammatory cytokine (IL-6, IL-1β, TNF-α) levels. γ-Glu-Tyr activates the cAMP/PKA signaling pathway and inhibits NF-κB phosphorylation, thereby reducing inflammatory responses. γ-Glu-Tyr can be used for research on type 2 diabetes and ulcerative colitis.

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.

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.

Anagliptin (SK-0403) is a highly selective, potent, orally active inhibitor of dipeptidyl peptidase 4 (DPP-4), with an IC₅₀ of 3.8 nM, and less selective at DPP-8 and DDP-9 with IC₅₀s of 68 nM and 60 nM, respectively.

Alogliptin Benzoate (SYR-322) 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 Benzoate can be used for the research of type 2 diabetes.

Trelagliptin (SYR-472) succinate 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).

Evogliptin (DA-1229) tartrate is an orally active DPP4 inhibitor with significant and sustained hypoglycaemic effects in mouse models. Evogliptin tartrate also inhibits the production of inflammatory and fibrotic signals in hepatocytes by inducing autophagy. Evogliptin tartrate can be used in studies of type 2 diabetes, osteoporosis, renal impairment and chronic liver inflammation.