product name GSK2636771
Description: GSK2636771 is a potent, orally bioavailable, PI3Kβ-selective inhibitor, that is sensitive to PTEN null cell lines. GSK2636771 is a selective PI3K inhibitor with targeting p110βand has different with the reported GDC-0941 which inhibits all class I PI3K isoforms. In breast cancer cell lines, treatment with GSK2636771 could significantly decrease the phosphorylation of AKT thus inhibits the cell viability. For EEC cell lines with PTEN-mutant, p110β inhibitor GSK2636771 should only combine with p110α selective inhibitor A66 to decrease cell viability.
References: Clin Cancer Res. 2013 Jul 1;19(13):3533-44.
433.42
Formula
C22H22F3N3O3
CAS No.
1372540-25-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 28 mg/mL (64.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Chemical Name
2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylbenzimidazole-4-carboxylic acid
other peoduct :
| In Vitro | Kinase Assay:
Cell Assay: Cells (p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines) are plated in 96-well microtiter plates at densities ranging from 1,500 to 15,000 cells/well, optimized for untreated control cells to be 80-90% confluent at the endpoint of the experiment. After 24 h, cells are treated with serial dilutions (100pM to 10μM) of GSK2636771. Cell viability is assessed after 72 h of treatment by incubation with CellTiter Blue for 1.5 h. The drug concentration requires for survival of 50% of cells relative to untreated cells (surviving fraction 50, SF50) is determined using GraphPad Prism version 5.0d. Cell lines that fails to achieve the SF50 to a given drug are nominally assigned as the highest concentration screened (i.e. 10μM). At least three independent experiments in triplicate per cell line targeted drug are performed. Association between a mutation and response to a targeted agent is determined using a Fisher’s exact test (GraphPad Prism), and a two-tailed P value <0.05 is considered statistically significant. GSK-2636771 shows selectively inhibitory activity in PTEN null cell lines (human prostate adenocarcinoma PC-3 and breast cancer HCC70) with EC50 of 36 nM and 72 nM, respectively. GSK2636771 significantly decreases cell viability in p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines, and leads to a marked decrease of AKT phosphorylation only in the control prostate and breast cancer cell lines. |
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| In Vivo | GSK-2636771 decreases phosphorylated protein kinase Akt (Ser473) levels in these xenograft models. GSK-2636771 (100 mg/kg) do not increase glucose/insulin levels in mice. |
| Animal model | |
| Formulation & Dosage | |
| References | Clin Cancer Res. 2013 Jul 1;19(13):3533-44. |
