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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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| 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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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
| 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 | |||
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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。
Efficacy and Cardiovascular Safety of DPP-4 Inhibitors
Dipeptidyl peptidase-4 (DPP-4) inhibitors or gliptins belong to the class of incretin mimetics. These drugs have been available on the market for the management of type 2 diabetes mellitus (T2DM) for over a decade. Sitagliptin, linagliptin, vildagliptin, saxagliptin and alogliptin are widely available globally, whilst anagliptin, gemigliptin and teneliptin are used mainly in the Asian countries. The glycemic control conferred by DPP-4 inhibitors varies among individual molecules with an average reduction of glycated hemoglobin (HbA1c) ranging between -0.5 to -1.0% with monotherapy. Additive effects on HbA1c reduction may result from combination therapy with other antidiabetics. Weak evidence from various studies suggests that DPP-4 inhibitors may be useful in treating nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). DPP-4 inhibitors safety is not established in pregnancy, and there is only meagre evidence of its use in T2DM among children. In line with the United States Food and Drug Administration (US FDA) recommendations, sitagliptin, linagliptin, saxagliptin and alogliptin have undergone rigorous cardiovascular outcome trials (CVOTs) in recent years, and the safety data for vildagliptin is available through retrospective analysis of various studies in meta-analysis. Small clinical trial, and meta-analysis based data are available for the CV safety of other DPP-4 inhibitors. In general, the CVOTs and other safety data do not reveal serious warning signals except for saxagliptin (higher risk of hospitalization from heart failure [hHF]), although there is no robust data on the risk of hHF among patients with moderate to severe HF at baseline treated with other DPP-4 inhibitors. This review critically appraises the efficacy and cardiovascular safety of DPP-4 inhibitors to empower clinicians to use this class of antidiabetic medications judiciously.
Drugs for type 2 diabetes
Alogliptin after acute coronary syndrome in patients with type 2 diabetes
Background: To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome.
Methods: We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.
Results: A total of 5380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P<0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, -0.36 percentage points; P<0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo.
Conclusions: Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo. (Funded by Takeda Development Center Americas; EXAMINE ClinicalTrials.gov number, NCT00968708.).
Alogliptin
Alogliptin was first approved by the FDA in January 2013 as a therapy to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). It is a dipeptidyl peptidase-4 (DPP-4) inhibitor used to improve glycemic control in conjunction with diet and exercise. This activity outlines the indications, mechanism, pharmacology, contraindications, and adverse events associated with alogliptin drug therapy.
Alogliptin
No information is available on the clinical use of alogliptin during breastfeeding. An alternate drug may be preferred, especially while nursing a newborn or preterm infant. Monitoring of the breastfed infant's blood glucose is advisable during maternal therapy with alogliptin.[1]