TG100-115
(Synonyms: 3,3'-(2,4-二氨基-6,7-蝶啶二基)二苯酚) 目录号 : GC15151
TG100-115 是一种选择性 PI3Kγ/PI3Kδ 抑制剂，IC50 分别为 83 和 235 nM。
Cas No.:677297-51-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Binding assays |
For PI3K assays, 40 ml of reaction buffer (20 mM Tris/4 mM MgCl2/10 mM NaCl, pH 7.4) containing 50 mM D-myo-phosphatidylinositol 4,5-bisphosphate substrate and the desired PI3K isoform were aliquoted to 96-well plates; kinase concentrations were 250-500 ng/well, such that linear kinetics were achieved over 90 min. The compound to be tested was then added as 2.5 ml of a DMSO stock to final concentration range of 100 mM to 1 nM. Reactions were initiated by addition of 10 ml of ATP to a final concentration of 3 mM, and after 90 min, 50 ml of Kinase-Glo reagent added to quantify residual ATP levels; luminosity was measured using an Ultra 384 instrument. Control reactions omitting either test compound or substrate were also performed. IC50 values were derived from experimental data by nonlinear curve fitting. |
| Cell experiment [1]: | |
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Cell lines |
Human umbilical vein EC |
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Preparation method |
The solubility of this compound in DMSO is >3.5mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
10 μM, 24-72 h |
|
Applications |
In HUVECs, TG100-115 (10 μM) inhibited the VEGF-induced increase of total level of VE-cadherin. TG100-115 inhibited VEGF mediated phosphorylation of mTOR and p70S6 kinase. TG100-115 (125 nM to 10 μM) inhibited FGF-stimulated phosphorylation of Akt. |
| Animal experiment [2]: | |
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Animal models |
Sprague–Dawley rats, Rodent and porcine myocardial ischemia (MI) models |
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Dosage form |
intravenous injection, 5 mg/kg |
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Application |
Pretreatment with TG100-115 (5 mg/kg) blocked both the edema and leukocytic infiltrate. In a rodent model of MI, TG100-115 (i.v. bolus 60 min after reperfusion) routinely reduced infarct size by ≥40%, with maximal efficacy reached by a dose of 0.5 mg/kg. In a porcine MI model, TG100-115 (0.5 mg/kg i.v. bolus 30 min after reperfusion) developed smaller infarcts. |
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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]. Palanki M S S, Dneprovskaia E, Doukas J, et al. Discovery of 3, 3 ‘-(2, 4-diaminopteridine-6, 7-diyl) diphenol as an isozyme-selective inhibitor of PI3K for the treatment of ischemia reperfusion injury associated with myocardial infarction[J]. Journal of medicinal chemistry, 2007, 50(18): 4279-4294. [2]. Doukas J, Wrasidlo W, Noronha G, et al. Phosphoinositide 3-kinase γ/δ inhibition limits infarct size after myocardial ischemia/reperfusion injury[J]. Proceedings of the National Academy of Sciences, 2006, 103(52): 19866-19871. |
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TG100-115 is an inhibitor of PI3Kγ and PI3Kδ with IC50 values of 83 nM and 235 nM, respectively. TG100-115 shows no obvious activity against PI3Kα and PI3Kβ [1].
TG100-115 remarkably reduced eosinophil accumulation, BALF levels of classic Th2 cytokine IL-13, perivascular and peribronchial leukocyte accumulations, and bronchiolar mucin accumulation in a murine model. Besides, TG100-115 showed to reduce airway hyper-responsiveness (AHR) by approximately 50% in asthmatic mice. Moreover, TG100-115 has been reported to reduce both smoke-and LPS-induced neutrophil and LPS-induced classic Th1 cytokine TNFα accumulations in mice [2].
References:
[1] Doukas J1, Wrasidlo W, Noronha G, Dneprovskaia E, Fine R, Weis S, Hood J, Demaria A, Soll R, Cheresh D. hosphoinositide 3-kinase gamma/delta inhibition limits infarct size after myocardial ischemia/reperfusion injury. Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19866-71.
[2] Doukas J1, Eide L, Stebbins K, Racanelli-Layton A, Dellamary L, Martin M, Dneprovskaia E, Noronha G, Soll R, Wrasidlo W, Acevedo LM, Cheresh DA. Aerosolized phosphoinositide 3-kinase gamma/delta inhibitor TG100-115 [3-[2,4-diamino-6-(3-hydroxyphenyl)pteridin-7-yl]phenol] as a therapeutic candidate for asthma and chronic obstructive pulmonary disease. J Pharmacol Exp Ther. 2009 Mar;328(3):758-65.
| Cas No. | 677297-51-7 | SDF | |
| 别名 | 3,3'-(2,4-二氨基-6,7-蝶啶二基)二苯酚 | ||
| 化学名 | 3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol | ||
| Canonical SMILES | C1=CC(=CC(=C1)O)C2=NC3=C(N=C2C4=CC(=CC=C4)O)N=C(N=C3N)N | ||
| 分子式 | C18H14N6O2 | 分子量 | 346.34 |
| 溶解度 | ≥ 3.46mg/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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.8873 mL | 14.4367 mL | 28.8734 mL |
| 5 mM | 0.5775 mL | 2.8873 mL | 5.7747 mL |
| 10 mM | 0.2887 mL | 1.4437 mL | 2.8873 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。