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5mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
PP-121 is a novel, potent and selective multi-targeted RTK (receptor tyrosine kinases) inhibitor that may have antitumor effects. It blocks a number of kinases, including DNA-PK, PDGFR, Hck, mTOR, VEGFR2, Src, and Abl, with respective IC50 values of 60 nM, 2 nM, 8 nM, 10 nM, 12 nM, and 18 nM. In vitro tests revealed strong antiproliferative activity, and in vivo tests revealed high antitumor efficacy.
Targets |
VEGFR2 (IC50 = 12 nM); PDGFR (IC50 = 2 nM); mTOR (IC50 = 10 nM); DNK-PK (IC50 = 60 nM); Src (IC50 = 14 nM)
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ln Vitro |
PP121 blocks the PI3K pathway by direct inhibition of PI3K/mTOR in two glioblastoma cell lines, U87 and LN229. A wide range of tumor cell lines with mutations in the PI3-K pathway members PIK3CA, PTEN, or RAS are effectively inhibited from proliferating by PP121. Most tumor cells are put into a G0G1 arrest by PP121. Src is directly inhibited by PP121 in cells, which also reverses the biochemical and morphological effects of Src. In vitro, PP121 effectively inhibits the Ret kinase domain (IC50<1 nM). The PI3-K and MAPK pathways are effectively blocked by PP121 when they are activated by VEGF. The fact that PP121 directly targets VEGFR2 in cells is supported by the fact that it inhibits VEGFR2 autophosphorylation at low nanomolar concentrations. In K562 cells and BaF3 cells that express Bcr-Abl, PP121 inhibits Bcr-Abl-induced tyrosine phosphorylation[1].
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ln Vivo |
Eca-109 xenograft growth is markedly inhibited by oral administration of PP121. PP121 or the vehicle treatment have no discernible impact on the body weights of mice. In xenograft tumors, oral administration of PP121 significantly reduces Akt-mTOR and NFkB activations. The administration of PP121 inhibits both p-IKKa/b and p-Akt Ser 473[2].
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Enzyme Assay |
Purified kinase domains are incubated with inhibitors (PP121) at 2- or 4-fold dilutions over a concentration range of 50- 0.001 M, or with a vehicle (0.1% DMSO), in the presence of 10 µM ATP, 2.5 µCi of γ- 32P-ATP, and substrate. Depending on the substrate, reactions are stopped by dotting onto nitrocellulose or phosphocellulose membranes. This membrane is then dried after being washed 5–6 times to remove any radioactivity that wasn't bound to it. Prism software is used to quantify transferred radioactivity through phosphorimaging, and IC50 values are generated by fitting the data to a sigmoidal dose-response curve[1].
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Cell Assay |
PP121 is applied to cells grown in 96-well plates at 4-fold dilutions (10 µM - 0.040 µM) or vehicle (0.1% DMSO). Cells are exposed to Resazurin sodium salt (22 µM) after 72 hours, and fluorescence is measured. Values for IC50 are computed. Non-adherent cells are plated at low density (3-5% confluence) and treated with drug (2.5 µM) or vehicle (0.1% DMSO) for proliferation assays involving single cell counting. Every day, cells are diluted in trypan blue and counted using a hemocytometer[1].
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Animal Protocol |
Mice: Eca-109 cells are injected into the axillary regions of nude mice (5×106 cells/mouse). When the tumor volumes reach around 200 mm3, the mice are randomly separated to three groups: Untreated control, PP121 (30 mg/kg) and vehicle (10% 1-methyl-2-pyrrolidinone and 90% PEG 300) group. Tumor volumes and the mice body weights are measured every 10 d[2].
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References |
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Molecular Formula |
C17H17N7
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Molecular Weight |
319.36378
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Exact Mass |
319.15454
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Elemental Analysis |
C, 63.93; H, 5.37; N, 30.70
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CAS # |
1092788-83-4
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Appearance |
Solid powder
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SMILES |
C1CCC(C1)N2C3=NC=NC(=C3C(=N2)C4=CN=C5C(=C4)C=CN5)N
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InChi Key |
NVRXTLZYXZNATH-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C17H17N7/c18-15-13-14(11-7-10-5-6-19-16(10)20-8-11)23-24(12-3-1-2-4-12)17(13)22-9-21-15/h5-9,12H,1-4H2,(H,19,20)(H2,18,21,22)
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Chemical Name |
1-cyclopentyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[3,4-d]pyrimidin-4-amine
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Synonyms |
PP121; PP-121; PP 121
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HS Tariff Code |
2934.99.9001
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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)
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Solubility (In Vitro) |
DMSO: ~64 mg/mL (~200.4 mM)
Water: <1 mg/mL Ethanol: ~2 mg/mL (~6.3 mM) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 3.1313 mL | 15.6563 mL | 31.3126 mL | |
5 mM | 0.6263 mL | 3.1313 mL | 6.2625 mL | |
10 mM | 0.3131 mL | 1.5656 mL | 3.1313 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.