Anagliptin (SK-0403) hydrochloride 是一种高选择性的、有效的、具有口服活性的二肽酰肽酶 4 (DPP-4) 抑制剂，IC50值为 3.8 nM，对DPP-8和DDP-9的选择性相对较弱，IC50值分别为 68 nM 和 60 nM。
| 生物活性 | Anagliptin (SK-0403) hydrochloride is a highly selective, potent, orally active inhibitor ofdipeptidyl peptidase4 (DPP-4), with anIC50of 3.8 nM, and less selective atDPP-8andDDP-9withIC50s of 68 nM and 60 nM, respectively[1]. |
| IC50& Target | DPP-4 3.8 nM (IC50) | DPP-9 60 nM (IC50) | DPP-8 68 nM (IC50) |
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体外研究
(In Vitro) | Anagliptin (SK-0403) (0-100 μM; 24 h) attenuates s-DPP-4-induced smooth muscle cells proliferation[2].
Anagliptin (100 μM; 10 min) reduces TNF-α production in cultured monocytes[2].
Anagliptin (0.001-10 μM; 24 h) significantly suppresses sterol regulatory element‐inding protein activity in HepG2 cells (21% decrease)[3].
Cell Proliferation Assay[2] | 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[2] | Cell Line: | Rat smooth muscle cells (SMC) | | Concentration: | 100 μM | | Incubation Time: | 10 min | | Result: | Blocked the early- but not the late-phase ERK phosphorylation induced by s-DPP-4. |
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体内研究
(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[2].
Anagliptin (0.3%; in diet; 4 weeks) exhibits a lipid‐lowering effect in a hyperlipidemic mice model[3].
| Animal Model: | Male apoliporotein E (apoE)-deficient mice[2] | | 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)[3] | | 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‐inding protein‐2 messenger ribonucleic acid expression level was significantly decreased at night. |
| Animal Model: | Male Sprague–Dawley rats and Beagle dogs[1] | | 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[1]
| Compound | Species | CLtot
(l/h/kg) | Vdss
(l/h/kg) | Cmaxc
(ng/ml) | Tmaxc
(h) | T1/2
(h) | AUC
(ng/h/ml) | BA
(%) | | Anagliptin hydrochloridea | Rat | 2.00 (iv) | 0.68 (iv) | 309 (62) (po) | 0.8 (2.3) (po) | 1.9 (po) | 1160 (po) | 23 (po) | | Dog | 0.65 (iv) | 0.83 (iv) | 261 (po) | 1.5 (po) | 1.0 (po) | 824 (po) | 100 (po) |
aAnagliptin hydrochloride dose in rats, 1 mg/kg, iv (n = 3); 10 mg/kg, po (n = 3). 4a dose in dogs, 0.2 mg/kg, iv (n = 3); 0.5 mg/kg, po (n = 2).cValues in parentheses were obtained at a dose of 3 mg/kg (n = 3). |
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| Clinical Trial | |
| 分子量 | |
| Formula | |
| CAS 号 | |
| 中文名称 | 阿拉格列汀盐酸盐；安奈格列汀盐酸盐；盐酸阿拉格列汀；盐酸安奈格列汀 |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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