TG100-115 |
| Catalog No.GC15151 |
PI3Kγ/PI3Kδ inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 677297-51-7
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
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.
| Kinase experiment [1]: | |
|
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]: | |
|
Cell lines |
Human umbilical vein EC |
|
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]: | |
|
Animal models |
Sprague–Dawley rats, Rodent and porcine myocardial ischemia (MI) models |
|
Dosage form |
intravenous injection, 5 mg/kg |
|
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. |
|
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. |
|
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. | |
| Cas No. | 677297-51-7 | SDF | |
| Chemical Name | 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 | ||
| Formula | C18H14N6O2 | M.Wt | 346.34 |
| Solubility | ≥ 3.46mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *