Linagliptin (BI-1356)
(Synonyms: 利格列汀; BI 1356) 目录号 : GC14827
A potent DPP-4 inhibitor
Cas No.:668270-12-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | EDTA plasma (20 μL) is diluted with 30 μL of DPP-4 assay buffer (100 mM Tris and 100 mM NaCl, adjusted to pH 7.8 with HCl) and mixed with 50 μL of H-Ala-Pro-7-amido-4-trifluoromethylcoumarin. The 200 mM stock solution in dimethylformamide is diluted 1:1000 with water to yield a final concentration of 100 μM. The plate is incubated at room temperature for 10 min, and fluorescence in the wells is determined by using a Victor 1420 Multilabel Counter at an excitation wavelength of 405 nm and an emission wavelength of 535 nm. For the detection of DPP-4 activity in wound lysates, 100 μg of protein from the respective wound lysates are used instead of 20 μL of plasma. Active GLP-1 is also detected from 100 μg of respective wound tissue samples and analyzed by using the Mouse/Rat Total Active GLP-1 Assay Kit. |
Cell experiment: | A total of 4.0×107 keratinocytes per well are seeded into 24-well plates. After reaching 50% confluence, cells are starved for 24 h with DMEM. Proliferation of cells is assessed by using 1 μCi/mL of [3H]methyl-thymidine in DMEM in the presence of 10% fetal bovine serum and increasing concentrations of linagliptin (3, 30, 300, or 600 nM) for 24 h. Cells are then washed twice with phosphate-buffered saline and incubated in 5% trichloroacetic acid at 4°C for 30 min, and the DNA is solubilized in 0.5mol/LNaOH for 30 min at 37°C. Finally, [3H]thymidine incorporation is determined. |
Animal experiment: | Each experimental group (vehicle or linagliptin treatment) consists of 10 individual ob/ob mice (n=10). Animals are treated orally once a day (8:00 AM) by gastrogavage using vehicle (1% methylcellulose) or linagliptin (3 mg/kg body weight in 1% methylcellulose) beginning 2 days (day−2) before wounding. After wounding, animals are subsequently treated once a day throughout the 10-day healing period. |
References: [1]. Eckhardt M, et al. 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 d | |
BI1356 is a potent and competitive DPP-4 inhibitor, which exhibited DPP-4 inhibiting activity in several independent tests with IC50 values of 0.4, 0.5, 0.9, and 1.1nM.[1]
DPP-4 is an N-terminal dipeptidyl exopeptidase existing as a membrane-bound protein and also as a soluble protein in plasma. It plays a major role in the degradation of incretins such as GLP-1 which is of great importance in the process of glucose metabolism. Under physiological conditions, GLP-1 is truncated by DPP-4 rapidly, which is located on the capillary endothelium proximal to the L-cells where GLP-1 is secreted in the ileum. GLP-1 could sensitize β-cells to glucose stimulation,consequently increasing intracellular cAMP concentrations in β-cells and accelerating and augmenting insulin response to absorb glucose. By being measured at the substrate at the binding site, BI1356 inhibits the DPP-4 enzyme.[1]
DPP-4 was extracted from confluent Caco-2 cells to determine the inhibition activity of BI1356. Assays were performed by mixing the inhibitor solution with substrates and the Caco-2 cell extract, which illustrated BI1356 inhibited DPP-4 with IC 50 values of 0.4, 0.5, 0.9, and 1.1 nM. BI1356 also possesses a very significant selectivity for DPP-4 relative to other dipeptidyl peptidases aminopeptidases N and P, prolyloligopeptidase, and the proteases trypsin, plasmin, and thrombin.[1]
An in vivo evaluation showed that BI1356 dose-dependently inhibited the DPP-4 enzyme in plasma within 30 min of administration. Separate doses ranging from 1 to 10 mg/kg achieved significant inhibition activity of DPP-4, which also showed persistent DPP-4 inhibition activity. The ED50 value for inhibition of plasma DPP-4 activity was calculated to be 0.9 mg/kg 24 h post dose. In a clinical study, BI1356 produced a remarkable, clinically meaningful and persistent improvement in glycaemic control, in accordance with enhanced parameters of β-cell function. Patients treated with BI1356 were more likely to achieve a reduction in HbA1c of ≥ 0.5% comparing control.[1,2]
References:
1.Thomas L, Eckhardt M, Langkopf E, et al. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3, 7-dihydro-purine-2, 6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors[J]. Journal of Pharmacology and Experimental Therapeutics, 2008, 325(1): 175-182.
2.Del Prato S, Barnett A H, Huisman H, et al. Effect of linagliptin monotherapy on glycaemic control and markers of β‐cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial[J]. Diabetes, Obesity and Metabolism, 2011, 13(3): 258-267.
| Cas No. | 668270-12-0 | SDF | |
| 别名 | 利格列汀; BI 1356 | ||
| 化学名 | 8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]purine-2,6-dione | ||
| Canonical SMILES | CC#CCN1C2=C(N=C1N3CCCC(C3)N)N(C(=O)N(C2=O)CC4=NC5=CC=CC=C5C(=N4)C)C | ||
| 分子式 | C25H28N8O2 | 分子量 | 472.5 |
| 溶解度 | ≥ 17.85 mg/mL in DMSO | 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 | 2.1164 mL | 10.582 mL | 21.164 mL |
| 5 mM | 0.4233 mL | 2.1164 mL | 4.2328 mL |
| 10 mM | 0.2116 mL | 1.0582 mL | 2.1164 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。