Anagliptin

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Anagliptin 是一种有效的 DPP-4 抑制剂（IC50 为 3.8 nM），用于治疗 2 型糖尿病。

Anagliptin is a potent Inhibitor of DPP-4(IC50 of 3.8 nM), for the treatment of type 2 diabetes mellitus.Soluble DPP-4 augmented cultured SMC proliferation, and anagliptin suppressed the proliferation by inhibiting ERK phosphorylation.?In THP-1 cells, anagliptin reduced lipopolysaccharide-induced TNF-α production with inhibiting ERK phosphorylation and nuclear translocation of nuclear factor-κB.?Quantitative analysis also showed that anagliptin reduced the area of atherosclerotic lesion in apoE-deficient mice.Treatment with anagliptin for 16 wk significantly reduced accumulation of monocytes and macrophages in the vascular wall, SMC content in plaque areas, and oil red O-stained area around the aortic valve without affecting glucose tolerance or body weight.?Serum DPP-4 concentrations were significantly higher in apoE-deficient mice than control mice, and the levels increased with aging, suggesting the involvement of DPP-4 in the progression of atherosclerosis. Anagliptin treatment significantly decreased the plasma total cholesterol (14% reduction, P < 0.01) and triglyceride levels (27% reduction, P < 0.01). Both low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol were also decreased significantly by anagliptin treatment. Sterol regulatory element-binding protein-2 messenger ribonucleic acid expression level was significantly decreased at night in anagliptin-treated mice (15% reduction, P < 0.05). Anagliptin significantly suppressed sterol regulatory element-binding protein activity in HepG2 cells (21% decrease, P < 0.001).(In Vitro):Anagliptin (SK-0403) (0-100 μM; 24 h) attenuates s-DPP-4-induced smooth muscle cells proliferation.Anagliptin (100 μM; 10 min) reduces TNF-α production in cultured monocytes.Anagliptin (0.001-10 μM; 24 h) significantly suppresses sterol regulatory element‐binding protein activity in HepG2 cells (21% decrease).(In Vivo):Anagliptin (SK-0403) (0.3%; in diet; 16 weeks) reduces atherosclerotic lesion and does not increase the number of circulating EPCs in apoliporotein E (apoE)-deficient mice.Anagliptin (0.3%; in diet; 4 weeks) exhibits a lipid‐lowering effect in a hyperlipidemic mice model.

Anagliptin (SK-0403) (0-100 μM; 24 h) attenuates s-DPP-4-induced smooth muscle cells proliferation.Anagliptin (100 μM; 10 min) reduces TNF-α production in cultured monocytes.Anagliptin (0.001-10 μM; 24 h) significantly suppresses sterol regulatory element‐binding protein activity in HepG2 cells (21% decrease). Cell Proliferation Assay Cell Line:Rat smooth muscle cells (SMC)Concentration:1, 10 and 100 μM Incubation Time:24 h Result:Attenuated s-DPP-4-induced SMC proliferation in a dose-dependent manner. Inhibited LPS-induced ERK phosphorylation and markedly suppressed LPS-induced nuclear translocation of NF-κBp65.Western Blot Analysis Cell Line:Rat smooth muscle cells (SMC) Concentration:100 μM Incubation Time:10 minResult:Blocked the early- but not the late-phase ERK phosphorylation induced by s-DPP-4.

Anagliptin (SK-0403) (0.3%; in diet; 16 weeks) reduces atherosclerotic lesion and does not increase the number of circulating EPCs in apoliporotein E (apoE)-deficient mice.Anagliptin (0.3%; in diet; 4 weeks) exhibits a lipid‐lowering effect in a hyperlipidemic mice model. Animal Model:Male apoliporotein E (apoE)-deficient mice Dosage:0.3% Administration:In diet, 16 weeks Result:Reduced DPP-4 activity in the plasma as expected and did not affect food consumption or body weight gain. Significantly reduced total cholesterol level, especially VLDL and LDL-C without affecting triglyceride level. Also decreased the α-SMA-positive area within the individual plaque.Animal Model: Male low‐density lipoprotein receptor‐deficient mice (B6.129S7‐Ldlrtm1Her/J)Dosage:0.3%Administration:In diet, 4 weeks Result:Significantly decreased the plasma total cholesterol (14% reduction) and triglyceride levels (27% reduction). Significantly decreased low‐density lipoprotein cholesterol and very low‐density lipoprotein cholesterol. Sterol regulatory element‐binding protein‐2 messenger ribonucleic acid expression level was significantly decreased at night.Animal Model:Male Sprague–Dawley rats and Beagle dogs Dosage:0.2, 0.5, 1 and 10 mg/kg Administration:Oral or intravenous administration (Pharmacokinetic Studies)Result:Selected PK parameters of Anagliptin hydrochloride in rats and dogs.

SK-0403

Metabolic Enzyme/Protease

DPP

DPP-4|DPP-8|DPP-9|

Metabolism;Cardiovascular system

Dipeptidyl-Peptidase 4 Inhibitors;LDL Cholesterol;Glycosylated Hemoglobin;Diabetes Mellitus;Coronary Disease

739366-20-2

383.45

C19H25N7O2

>98% (HPLC)

DMSO:95mg/ml (247.75 Mm; Need ultrasonic)

CC1=NN2C=C(C=NC2=C1)C(=O)NCC(C)(C)NCC(=O)N1CCC[C@H]1C#N

——

(-20℃)

With Ice Pack

≥ 2 years