GSK2636771 is a potent and selective, orally bioavailable inhibitor of phosphatidylinositol 3-kinase-beta (PI3Kβ) for the treatment of PTEN deficient tumors. GSK2636771 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 decreases phosphorylated protein kinase Akt (Ser473) levels in these xenograft models. GSK2636771 (100 mg/kg) do not increase glucose/insulin levels in mice. GSK2636771 is currently in Phase I/II trials.
Cancer Cell. 2015 Jan 12;27(1):97-108.
|Source||Cancer Cell (2015). Figure 3. GSK2636771 (Abmole)|
|Method||Tumor growth assay|
|Concentrations||30mg/kg per oral gavage daily|
|Incubation Time||21 days|
|Results||Both BYL719 and GSK2636771, a structurally unrelated p110b inhibitor currently in clinical trials, slowed tumor growth but only the combination induced tumor shrinkage.|
|Source||Cancer Cell (2015). Figure 3.GSK2636771 (Abmole)|
|Cell Lines||BT-474, SKBR3 cell|
|Incubation Time||24 h|
|Results||This led to the loss of p110b recruitment and the block of the rebound of AKT activation observed 24 hr after treatment with BYL719 alone.|
|Cell lines||EEC cell lines|
|Preparation method||Cells were 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 24h, cells were treated with serial dilutions (100pM to 10μM) of PI3K and MAPK pathway inhibitors (Supplementary Methods, Supplementary Table 3). Cell viability was assessed after 72h of treatment by incubation with CellTiter Blue (Promega, Southampton, UK) for 1.5h.|
|Concentrations||100pM to 10μM|
|Animal models||6- to 8-week-old female athymic nude mice BT474 tumor model|
|Formulation||GSK2636771 was dissolved on 0.5% metilcellulose and 0.2% Tween 80.|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 80 mg/mL|
|Related PI3K Products|
Bimiralisib (PQR309) is an orally bioavailable inhibitor of PI3K and mTOR, with potential antineoplastic activity.
PIK-III (also known as VPS34-IN2) is a potent and selective inhibitor of VPS34 enzymatic activity, with IC50s of 18 nM and 1.2 μM for VPS34 and PI(3)Kδ, respectively.
LY3023414 is a selective ATP-competitive inhibitor of PI3Kα and mTOR, DNA-PK, and other class I PI3K family members.
SAR405 is a PIK3C3/Vps34 inhibitor with an IC50 of 1.2 nM. SAR405 also is a proximal inhibitor of the autophagy machinery.
Tenalisib (RP6530) is a potent and selective dual PI3Kδ/γ inhibitor with IC50 values of 24.5 nM and 33.2 nM for PI3Kδ and PI3Kγ, respectively. Its selectivity over α and β isoforms are more than 300-fold and 100-fold, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.