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Description: CCT128930 is a novel, potent, ATP-competitive and selective pyrrolopyrimidine-based inhibitor of Akt2 (IC50 = 6 nM in a cell-free assay) with potential anticancer activity. It showed 28-fold greater selectivity for Akt2 over the closely related PKA kinases. CCT128930 was discovered through fragment- and structure-based drug design approaches. CCT128930 exhibited marked antiproliferative activity and inhibited the phosphorylation of a range of AKT substrates in multiple tumor cell lines in vitro, consistent with AKT inhibition. In conclusion, CCT128930 is a novel, potent and selective AKT inhibitor that blocks AKT activity in vitro and in vivo and induces marked antitumor responses.
References: Mol Cancer Ther. 2011 Feb;10(2):360-71.
Product Catalog 2023
Guide to Product Handling
Synonym: CCT128930; CCT-128930; CCT 128930.
Chemical Name: 4-(4-chlorobenzyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-amine
SMILES Code: NC1(CC2=CC=C(Cl)C=C2)CCN(C3=C4C(NC=C4)=NC=N3)CC1
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
Kinase Assay: Profiling against 50 different human kinases is carried out using 10 μM CCT128930 at an ATP concentration equivalent to the Km for each enzyme.
Cell Assay: Cells (U87MG, LNCaP and PC3 cells) are seeded in 96-well plates and allowed to attach for 36 hours to ensure exponential growth prior to treatment. In vitro antiproliferative activity is determined using a 96-hour SRB assay. TCA-fixed cells are stained for 30 minutes with 0.4% (wt/vol) SRB dissolved in 1% acetic acid. At the end of the staining period, SRB is removed and cultures are quickly rinsed four times with 1% acetic acid to remove unbound dye. The acetic acid is poured directly into the culture wells from a beaker. This procedure permits rinsing to be performed quickly so that desorption of protein-bound dye does not occur. Residual wash solution is removed by sharply flicking plates over a sink, which ensures the complete removal of rinsing solution. Because of the strong capillary action in 96-well plates, draining by gravity alone often fails to remove the rinse solution when plates are simply inverted. After being rinsed, the cultures are air dried until no standing moisture is visible. Bound dye is solubilized with 10 mM unbuffered Tris base (pH 10.5) for 5 minutes on a gyratory shaker. OD is read in either a UVmax microtiter plate reader or a Beckman DU-70 spectrophotometer. For maximum sensitivity, OD is measured at 564 nm. Because readings are linear with dye concentrations only below 1.8 OD units, however, suboptimal wavelengths are generally used, so that all samples in an experiment remains within the linear OD range. With most cell lines, wavelengths of approximately 490-530 nm works well for this purpose.
CCT128930 exhibits marked antiproliferative activity against PTEN-deficient human tumor cell lines including U87MG human glioblastoma cells, LNCaP human prostate cancer cells and PC3 human prostate cancer cells with GI50 of 6.3 μM, 0.35 μM and 1.9 μM, respectively. Furthermore, CCT128930 causes a G1 arrest in PTEN-null U87MG human glioblastoma cells and Akt pathway blockade.
[1] Yap TA, et al. Mol Cancer Ther. 2011, 10(2), 360-371.
Purity ≥98%
COA
MSDS
NMR
Effect of CCT128930 exposure on expression of AKT biomarkers and cell cycle proteins in a panel of human tumor cell lines. Mol Cancer Ther. 2011, 10(2), 360-371.
Pharmacokinetic behavior and pharmacodynamic effects of CCT128930 in vivo.
Antitumor activity of CCT128930 in human tumor xenografts.