| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Torkinib (also known as PP242) is a novel, potent and selective ATP-competitive mTOR (mammalian target of rapamycin) inhibitor with potential anticancer activity.In cell-free assays, it inhibits mTOR with an IC50 of 8 nM; additionally, it targets both mTOR complexes (mTORC) more selectively than PI3Kδ or PI3Kα/β/γ, respectively, by >10- and 100-fold. The deactivation of the mammalian target of rapamycin complex 2/AKT1 signaling pathway by torkinib inhibits the proliferation and migration of bladder cancer cells. A pheochromocytoma PC12 cell tumor model demonstrates PP242's potent antitumor activity. By blocking the PI3K/AKT/mTOR pathway, PP242 prevents gastric cancer from proliferating, metastasizing, and forming new blood vessels.
| Targets |
mTOR (IC50 = 8 nM); mTORC1 (IC50 = 30 nM); mTORC2 (IC50 = 58 nM); p110δ (IC50 = 100 nM); PDGFR (IC50 = 410 nM); DNA-PK (IC50 = 410 nM); p110γ (IC50 = 1.3 μM); p110α (IC50 = 2 μM); p110β (IC50 = 2.2 μM); Hck (IC50 = 1.2 μM); Scr (IC50 = 1.4 μM); VEGFR2 (IC50 = 1.5 μM); Abl (IC50 = 3.6 μM); EphB4 (IC50 = 3.4 μM); EGFR (IC50 = 4.4 μM); Scr(T338I)(IC50 = 5.1 μM); Autophagy; Mitophagy
|
|---|---|
| ln Vitro |
PP242 exhibits potent selectivity for mTOR over other PI3K family kinases such as p110α, p110β, p110γ, p110δ, and DNA-PK with IC50 of 1.96 μM, 2.2 μM, 1.27 μM, 0.102 μM, and 0.408 μM, respectively. Ret, PKCα, PKCβ, and JAK2 are among the protein kinases that PP242 shows some inhibitory activity against, while 215 other protein kinases are the targets of remarkable selectivity displayed by PP242. PP242 inhibits mTORC1 and mTORC2 in the same way that rapamycin does not. Treatment with PP242 (00.04-10 μM)inhibits Akt, p70S6K, a substrate of mTOR, and S6, a downstream target of S6, in BT549 cells in a dose-dependent manner.[1] PP242 has an IC50 of 49 nM and can effectively inhibit PKC. Low concentrations of PP242 prevent Akt S473 from being phosphorylated, and higher concentrations also partially prevent Akt T308-P from being phosphorylated. PP242 inhibits the proliferation of primary MEFs and the phosphorylation of 4EBP1 at T36/45 and S65 more potently than rapamycin because it is a more potent mTORC1 inhibitor. By causing more binding between 4EBP1 and eIF4E than rapamycin, PP242 potently inhibits cap-dependent translation but not rapamycin.[2] PP242 potently inhibits the proliferation of p190-transformed murine BM, SUP-B15, and K562 cells with GI50 of 12 nM, 90 nM, and 85 nM, respectively. With GI50 values of 0.49 μM, 0.19 μM, 2.13 μM, and 1.57 μM, respectively, PP242 also prevents the growth of solid tumor cell lines like SKOV3, PC3, 786-O, and U87. [3] Inducing cytoreduction and apoptosis in multiple myeloma (MM) cells with PP242 is also more successful than rapamycin. [4]
|
| ln Vivo |
In the liver and fat of mice, administration of PP242 is able to completely inhibit the phosphorylation of Akt at S473 and T308. Despite having the ability to completely inhibit the phosphorylation of 4EBP1 and S6, PP242 only partially inhibits the phosphorylation of Akt in skeletal muscle and is more effective at inhibiting the phosphorylation of T308 than S473. Oral administration By inhibiting mTORC2 and mTORC1 activation, which are correlated with cell-size loss, PP242 effectively delays the onset of leukemia in the mice model and causes leukemia regression. [3] Giving mice PP242 treatment effectively inhibits the growth of 8226 cells.[4]
|
| Enzyme Assay |
Recombinant mTOR is incubated with PP242 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 -32P-ATP), and 3 μg/mL BSA at 2-fold dilutions over a concentration range of 50-0.001 μM . The substrate is rat recombinant PHAS-1/4EBP1 (2 mg/mL). Spotting onto nitrocellulose after it has been washed with 1 M NaCl and 1% phosphoric acid (roughly six times, each for five to ten minutes) ends the reaction. The transferred radioactivity is measured by phosphorimaging after the sheets have dried. Using the Prism software program, the IC50 value is determined by fitting the data to a sigmoidal dose-response curve.
|
| Cell Assay |
In 96-well plates, cells are subjected to increasing concentrations of PP242 for 72 hours. Each well receives 10 μL of 440 μM resazurin sodium salt after 72 hours of treatment, and after 18 hours, the amount of florescence in each well is determined using a top-reading fluorescent plate reader with excitation at 530 nm and emission at 590 nm.
|
| Animal Protocol |
Mice: Male C57BL/6 mice that are six weeks old are fasted the night before receiving medication. Rapamycin (0.1 mg), Torkinib (PP 242) (0.4 mg), or the vehicle alone is injected IP. 250 mU of insulin in 100 L of saline is injected intraperitoneally (IP) after 30 min for the Rapamycin-treated mouse or 10 min for the Torkinib (PP 242) and vehicle-treated mice. The mice are killed by cervical dislocation and CO2 asphyxiation 15 minutes after receiving an insulin injection. In 200 μL of cap lysis buffer, tissues are harvested and frozen on liquid nitrogen. The frozen tissue is manually broken up with a mortar and pestle, defrosted on ice, and then given one last processing step with a micro tissue-homogenizer. Bradford assay is used to determine the cleared lysate's protein concentration, and a Western blot is used to examine 5-10 μg of protein.
|
| References |
| Molecular Formula |
C16H16N6O
|
|
|---|---|---|
| Molecular Weight |
308.3378
|
|
| Exact Mass |
308.13856
|
|
| Elemental Analysis |
C, 62.32; H, 5.23; N, 27.26; O, 5.19
|
|
| CAS # |
1092351-67-1
|
|
| Related CAS # |
|
|
| Appearance |
Solid powder
|
|
| SMILES |
O([H])C1C([H])=C([H])C2=C(C=1[H])C([H])=C(C1C3=C(N([H])[H])N=C([H])N=C3N(C([H])(C([H])([H])[H])C([H])([H])[H])N=1)N2[H]
|
|
| InChi Key |
MFAQYJIYDMLAIM-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C16H16N6O/c1-8(2)22-16-13(15(17)18-7-19-16)14(21-22)12-6-9-5-10(23)3-4-11(9)20-12/h3-8,20,23H,1-2H3,(H2,17,18,19)
|
|
| Chemical Name |
2-(4-Amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol
|
|
| Synonyms |
Torkinib; PP-242; PP242; PP 242
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~62 mg/mL (~201.1 mM)
Water: <1 mg/mL Ethanol: ~18 mg/mL (~58.4 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.11 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2432 mL | 16.2159 mL | 32.4317 mL | |
| 5 mM | 0.6486 mL | 3.2432 mL | 6.4863 mL | |
| 10 mM | 0.3243 mL | 1.6216 mL | 3.2432 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
