PP242 (Synonyms: PP242; PP-242) |
カタログ番号GC15904
One-Click Copy Product Info
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PP242 (PP 242) は、選択的かつ ATP 競合的な mTOR 阻害剤であり、IC50 は 8 nM です。 PP242 は、mTORC1 と mTORC2 の両方をそれぞれ 30 nM と 58 nM の IC50 で阻害します。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1092351-67-1
Sample solution is provided at 25 µL, 10mM.
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PP242, a novel potent and selective mTOR inhibitor, can inhibit the active site of mTOR kinase in both mTORC1 and mTORC2 with IC50 of 8 nM.
The mammalian target of rapamycin (mTOR), a serine-threonine kinase, is present in two protein complexes, mTORC1 and mTORC2, that have distinct subunit composition, substrates and mechanisms of activation.
Treatment of PP242 was shown to lead to the death of certain mouse and human leukemia cells [1]. In primary AML cells and CD34+ progenitor cells, PP242 can inhibit the activity of mTOR and their downstream targets, therefore inducing cell apoptosis [2].
The component has also been used to study the role of COX-2 in vivo. In models of acute leukemia harboring the Philadelphia chromosome (Ph) translocation, PP242 can delay the onset of leukemia and augment the effects of front-line tyrosine kinase inhibitors more effectively, thereby suppressing the expansion of leukemia [1]. In addition, PP242 was shown to suppresse leukemia progression in a murine leukemia model which was driven by mutated FLT3 with constitutive activation of mTOR [2].
References:
1.Janes MR, Limon JJ, So L, Chen J, Lim RJ, Chavez MA, et al. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat Med 2010,16:205-213.
2.Zeng Z, Shi YX, Tsao T, Qiu Y, Kornblau SM, Baggerly KA, et al. Targeting of mTORC1/2 by the mTOR kinase inhibitor PP242 induces apoptosis in AML cells under conditions mimicking the bone marrow microenvironment. Blood 2012,120:2679-2689.
| Kinase experiment [1]: | |
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In vitro mTOR (FRAP1) kinase assay |
Recombinant mTOR was incubated with PP242 at 2-fold dilutions over a concentration range of 50 ~ 0.001 μM in an assay containing 50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween, 10 μM ATP (2.5 μCi of γ-32P-ATP), and 3 μg/mL BSA. Rat recombinant PHAS-1/4EBP1 (2 mg/mL) was used as a substrate. Reactions were terminated by spotting onto nitrocellulose, which was washed with 1 M NaCl/1% phosphoric acid (approximately 6 times, 5 ~ 10 mins each). Sheets were dried and the transferred radioactivity was quantitated by phosphorimaging. IC50 value was calculated by fitting the data to a sigmoidal dose-response curve using the Prism software package. |
| Cell experiment [2]: | |
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Cell lines |
AML cells |
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Preparation method |
The solubility of this compound in DMSO is ≥61.6mg/mL. 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 |
0.1, 0.2, 0.6, 1.7 or 5.0 μM; 48 hrs |
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Applications |
In primary AML cells cultured alone or cocultured with stromal cells, PP242 dose-dependently induced apoptosis. In addition, PP242 induced apoptosis in CD34＋ AML progenitor cells cultured under the above-mentioned conditions. |
| Animal experiment [2]: | |
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Animal models |
Ba/F3-ITD/luc/GFP mouse model of leukemia |
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Dosage form |
60 mg/kg, p.o.; every other day |
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Applications |
At the dose of 60 mg/kg, PP242 reduced leukemia burden. In addition, The anti-leukemia effect of PP242 was greater than that of Rapamycin at the dose of 0.5 mg/kg (the tolerable dose that was previously shown to inhibit mTOR signaling). |
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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]. Apsel B, Blair JA, Gonzalez B, Nazif TM, Feldman ME, Aizenstein B, Hoffman R, Williams RL, Shokat KM, Knight ZA. Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9. [2]. Zeng Z, Shi YX, Tsao T, Qiu Y, Kornblau SM, Baggerly KA, et al. Targeting of mTORC1/2 by the mTOR kinase inhibitor PP242 induces apoptosis in AML cells under conditions mimicking the bone marrow microenvironment. Blood 2012,120:2679-2689. | |
| Cas No. | 1092351-67-1 | SDF | |
| 同義語 | PP242; PP-242 | ||
| Chemical Name | (2E)-2-(4-amino-1-propan-2-yl-2H-pyrazolo[3,4-d]pyrimidin-3-ylidene)indol-5-ol | ||
| Canonical SMILES | CC(C)N1C2=C(C(=C3C=C4C=C(C=CC4=N3)O)N1)C(=NC=N2)N | ||
| Formula | C16H16N6O | M.Wt | 308.35 |
| 溶解度 | ≥ 61.6mg/mL in DMSO, ≥ 31mg/mL in EtOH | 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.2431 mL | 16.2153 mL | 32.4307 mL |
| 5 mM | 648.6 μL | 3.2431 mL | 6.4861 mL |
| 10 mM | 324.3 μL | 1.6215 mL | 3.2431 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 saline, 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: >98.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 12 reference(s) in Google Scholar.)