TGX-221 |
| Catalog No.GC15935 |
PI3Kβ inhibitor,potent,selective and ATP competitive
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 663619-89-4
Sample solution is provided at 25 µL, 10mM.
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TGX-221 is a potent inhibitor of (phosphatidylinositol 3-kinases) PI3K which specifically inhibits PI3K -p110β isoform with IC50 value of 8.5 nM [1].
In J774.2 macrophage cells, TGX-221 has been demonstrated to reduce insulin-induced phosphorylation of Ser473 of protein kinase B (PKB). While in in CHO-IR and 3T3-L1 cells, TGX-221 has no effect on PKB phosphprylation [1].
In vivo, TGX-221 significantly improved blood flow in FeCl3-induced arterial thrombosis as well as increased tail and renal bleeding times in mice. In addition, TGX-221 has revealed to disrupt CFRs in a Folts model of arterial thrombosis in male Sprague-Dawley rats [2].
Reference:
[1] Chaussade C1, Rewcastle GW, Kendall JD, Denny WA, Cho K, Gr nning LM, Chong ML, Anagnostou SH,Jackson SP, Daniele N, Shepherd PR. Evidence for functional redundancy of class IA PI3K isoforms in insulin signalling. Biochem J. 2007 Jun 15;404(3):449-58.
[2] Bird JE1, Smith PL, Bostwick JS, Shipkova P, Schumacher WA. Bleeding response induced by anti-thrombotic doses of a phosphoinositide 3-kinase (PI3K)-β inhibitor in mice. Thromb Res. 2011 Jun;127(6):560-4.
| Kinase experiment [1]: | |
|
Lipid kinase activity |
IC50 values were measured using a standard lipid kinase activity with PI as a substrate. The differences were that (i) 100 μM cold ATP was used instead of 10 μM, (ii) the DMSO concentration was 1% rather than 2%, and (iii) [γ-33P]ATP was used instead of [γ-32P]ATP. The TLC plates were quantified using a phosphorimager screen. The reported IC50 values were determined by non-linear regression analysis on the basis of at least three independent experiments repeated across multiple preparations of recombinant protein. |
| Cell experiment [2]: | |
|
Cell lines |
PC3 cells |
|
Preparation method |
The solubility of this compound in DMSO is >68.7mg/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. |
|
Reaction Conditions |
0.2, 2 and 20 μM; 24 ~ 72 hrs |
|
Applications |
In PC3 cells, TGX-221 treatment (0.2, 2, and 20 μM) inhibited cell proliferation, and significantly reduced the activity of the p110β PI3K isoform. |
| Animal experiment [3]: | |
|
Animal models |
FeCl3-induced arterial thrombosis in mice |
|
Dosage form |
0.3 + 0.3, 1 + 1, 3 + 3 mg/kg + mg/kg/hr; i.v. |
|
Applications |
At the doses of 1 + 1 (49 % ± 13.9%) and 3 + 3 (88 % ± 10.6%), TGX-221 improved integrated blood flow over 30 mins in a mouse model. In addition, Tail bleeding time (BT) (sec) increased with TGX-221 doses of 3 + 3 (median 1560) and 1 + 1 (1305). In all TGX-221 groups, mean renal BT (sec) also increased. |
|
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]. Chaussade C, Rewcastle GW, Kendall JD, Denny WA, Cho K, Gr?nning LM, Chong ML, Anagnostou SH, Jackson SP, Daniele N, Shepherd PR. Evidence for functional redundancy of class IA PI3K isoforms in insulin signalling. Biochem J. 2007 Jun 15;404(3):449-58. [2]. Straub A, Wendel HP, Dietz K, Schiebold D, Peter K, Schoenwaelder SM, Ziemer G. Selective inhibition of the platelet phosphoinositide 3-kinase p110beta as promising new strategy for platelet protection during extracorporeal circulation. Thromb Haemost. 2008 Mar;99(3):609-15. [3]. Bird JE, Smith PL, Bostwick JS, Shipkova P, Schumacher WA. Bleeding response induced by anti-thrombotic doses of a phosphoinositide 3-kinase (PI3K)-β inhibitor in mice. Thromb Res. 2011 Jun;127(6):560-4. | |
| Cas No. | 663619-89-4 | SDF | |
| Chemical Name | 9-(1-anilinoethyl)-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one | ||
| Canonical SMILES | CC1=CN2C(=O)C=C(N=C2C(=C1)C(C)NC3=CC=CC=C3)N4CCOCC4 | ||
| Formula | C21H24N4O2 | M.Wt | 364.44 |
| Solubility | ≥ 68.7mg/mL in DMSO with gentle warming | 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 | 2.7439 mL | 13.7197 mL | 27.4394 mL |
| 5 mM | 548.8 μL | 2.7439 mL | 5.4879 mL |
| 10 mM | 274.4 μL | 1.372 mL | 2.7439 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 26 reference(s) in Google Scholar.)
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