Anagliptin (SK-0403) 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) 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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(260.79 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.6079 mL | 13.0395 mL | 26.0790 mL | | 5 mM | 0.5216 mL | 2.6079 mL | 5.2158 mL | | 10 mM | 0.2608 mL | 1.3040 mL | 2.6079 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
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此方案可获得 ≥ 2.5 mg/mL (6.52 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (6.52 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.52 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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