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].
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| IC50& Target |
DPP-4 3.8 nM (IC50) |
DPP-9 60 nM (IC50) |
DPP-8 68 nM (IC50) |
|
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. |
|
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 |
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| 分子量 |
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| Formula |
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| CAS 号 |
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| 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.
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| 储存方式 |
Please store the product under the recommended conditions in the Certificate of Analysis.
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