Alogliptin (SYR-322)
(Synonyms: 阿格列汀; SYR-322 free base) 目录号 : GC15130
Alogliptin (SYR-322) (SYR-322 free base) 是一种有效的、选择性的、具有口服活性的 DPP-4 抑制剂，IC50 <10 nM，选择性比 DPP-8 和 DPP-9 高 10,000 倍以上.
Cas No.:850649-61-5
Sample solution is provided at 25 µL, 10mM.
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Alogliptin (also known as SYR-322), is a novel, orally-available and highly selective quinazolinone-based inhibitor of dipeptidyl peptidase-4 (DPP-4), a serine aminopeptidase catalyzing the cleavage of peptides, that potently inhibits human DPP-4 in vitro with 50% inhibition concentration IC50 value of 6.9 nM and barely exhibits any inhibition towards the closely related serine proteases, including DPP-2, DPP-8, DPP-9, fibroblast activation protein/seprase, prolyl endopeptidas and tryptase (IC50 > 100,000 nM for all). Alogliptin prevents DPP-4-catalyzed degradation of GLP-1 and GIP, which regulate concentrations of blood glucose by stimulating glucose-dependent insulin secretion, and hence is being investigated in the treatment of type 2 diabetes.
Reference
[1].Bumsup Lee, Lihong Shi, Daniel B. Kassel, Tomoko Asakawa, Koji Takeuchi and Ronald J. Christopher. Pharmacokinetic, pharmacodynamics, and efficacy profiles of alogliptin, a novel inhibitor of dipeptidyl peptidase-4, in rats, dogs, and monkeys. European Journal of Pharmacology 589 (2008) 306-314
| Cell experiment: [1] | |
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Cell lines |
U937 histiocyte |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
5 nM, 48h, inhibited cell proliferation 1 nM, 48h, inhibited MMP-1 secretion |
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Applications |
Alogliptin inhibited cell proliferation by 53% at concentration of 5 nM. At 1 nM, alogliptin inhibited MMP-1 secretion significantly, suggesting that the inhibitory effect of alogliptin on MMP is not associated with that on cell proliferation. |
| Animal experiment : [2] | |
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Animal models |
Zucker fa/fa rats |
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Dosage form |
Eight-week-old male Zucker fa/fa rats were divided into 5 groups based on body weight and fasting plasma glucose levels and administered vehicle alone (0.5% carboxymethylcellulose) or alogliptin at 0.3, 1, 3, or 10 mg/kg by single bolus oral gavage (5 ml/kg dose volume). At 30 min postdose, rats were given a glucose solution (1 g/kg, 2ml/kg dose volume). Blood glucose concentrations were analyzed up to 90min after glucose load using the Accu-Chek glucometer and plasma insulin concentrations were analyzed up to 60 min after glucose load using an insulin ELISA kit. |
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Applications |
Early-phase insulin secretion was increased after a single dose of alogliptin compared with vehicle alone. Alogliptin increased about 1.5, 1.5, and 1.8 fold for the 0.3, 1, and 3 mg/kg doses. Significant decreases in blood glucose excursion were observed for all alogliptin doses compared with vehicle alone after an oral glucose load. Mean baseline-adjusted blood glucose AUC0–90 min was decreased by approximately 31%, 37%, and 41% for the 0.3, 1, and 3 mg/kg doses, respectively. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Ta N N, Li Y, Schuyler C A, et al. DPP-4 (CD26) inhibitor alogliptin inhibits TLR4-mediated ERK activation and ERK-dependent MMP-1 expression by U937 histiocytes. Atherosclerosis, 2010, 213(2): 429-435. [2] Lee B, Shi L, Kassel D B, et al. Pharmacokinetic, pharmacodynamic, and efficacy profiles of alogliptin, a novel inhibitor of dipeptidyl peptidase-4, in rats, dogs, and monkeys. European journal of pharmacology, 2008, 589(1): 306-314. |
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| Cas No. | 850649-61-5 | SDF | |
| 别名 | 阿格列汀; SYR-322 free base | ||
| 化学名 | 2-[[6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxopyrimidin-1-yl]methyl]benzonitrile | ||
| Canonical SMILES | CN1C(=O)C=C(N(C1=O)CC2=CC=CC=C2C#N)N3CCCC(C3)N | ||
| 分子式 | C18H21N5O2 | 分子量 | 339.39 |
| 溶解度 | ≥ 14.75 mg/mL in DMSO, ≥ 100 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.9465 mL | 14.7323 mL | 29.4646 mL |
| 5 mM | 0.5893 mL | 2.9465 mL | 5.8929 mL |
| 10 mM | 0.2946 mL | 1.4732 mL | 2.9465 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet