|PP121 Catalog No.GC11003|
Sample solution is provided at 25 µL, 10mM.
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Purified kinase domains are incubated with inhibitors (PP121) at 2- or 4-fold dilutions over a concentration range of 50- 0.001 µM or with vehicle (0.1% DMSO) in the presence of 10 µM ATP, 2.5 µCi of γ- 32P-ATP and substrate. Reactions are terminated by spotting onto nitrocellulose or phosphocellulose membranes, depending on the substrate; this membrane is then washed 5-6 times to remove unbound radioactivity and dried. Transferred radioactivity is quantitated by phosphorimaging and IC50 values are calculated by fitting the data to a sigmoidal doseresponse using Prism software.
Cells grown in 96-well plates are treated with PP121 at 4-fold dilutions (10 µM - 0.040 μM) or vehicle (0.1% DMSO). After 72 h cells are exposed to Resazurin sodium salt (22 µM) and fluorescence is quantified. IC50 values are calculated. For proliferation assays involving single cell counting, non-adherent cells are plated at low density (3–5% confluence) and treated with drug (2.5 µM) or vehicle (0.1% DMSO). Cells are diluted into trypan blue daily and viable cells counted using a hemocytometer.
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.
. Apsel B, et al. Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol, 2008, 4(11), 691-699.
|Solubility||≥15.95mg/mL in DMSO||Storage||Store at -20°C|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|
|Shipping Condition||Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
PP121 is a dual inhibitor of tyrosine and phosphoinositide kinases .
PP121 is found to inhibit both tyrosine kinases and PI3-Ks but not serine-threonine kinases. It potently inhibits p110α, p110β, p110γ, p110δ, DNA-PK and mTOR with IC50 values of 52nM, 1.4μM, 1.1μM, 150nM, 60nM and 10nM, respectively. For the tyrosine kinases, PP121 shows inhibition with IC50 values of 21nM, 4nM, 10nM,55nM, 550nM, 220nM and <1nM for Ab1, Hck, Src, VEGFR2, EGFR, EphB4 and PDGFR, respectively .
In cells, PP121 can reverse v-Src mediated cellular transformation and restore actin stress fiber staining. PP121 also potently inhibits the mutant Ret kinase with IC50 value less than 1nM in thyroid tumors34. Furthermore, PP121 is found to evade drug resistance through redundantly targeting Bcr-Abl mediated cell survival and PI3-K/mTOR mediated cell proliferation .
 Apsel B, Blair J A, Gonzalez B, et al. Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nature chemical biology, 2008, 4(11): 691-699.