GSK2126458 is a highly selective and potent inhibitor of PI3K with Ki of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM for p110α/β/δ/γ, mTORC1/2 , respectively.

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

GSK2126458; GSK458

白色至黄色固体

DMSO : 100 mg/mL (197.82 mM)

mTORC1; p110α; p110β; p110γ; p110δ

GSK2126458 potently inhibits the activity of common activating mutants of p110α (E542K, E545K, and H1047R) found in human cancer with Ki of 8 pM, 8 pM and 9 pM, respectively. GSK2126458 causes a significant reduction in the levels of pAkt-S473 with remarkable potency in T47D and BT474 cells with IC50 of 0.41 nM and 0.18 nM, respectively. Furthermore, GSK2126458 leads to a G1 cell cycle arrest and produces the inhibitory effect on cell proliferation in a large panel of cell lines, including T47D and BT474 breast cancer lines with IC50 of 3 nM and 2.4 nM, respectively. The combination of GSK2118436 or GSK1120212 with GSK2126458 enhances cell growth inhibition and decreases S6 ribosomal protein phosphorylation in drug-resistant clones from the A375 BRAF(V600E) and the YUSIT1 BRAF(V600K) melanoma cell lines. GSK2126458 potentiates the antiproliferative activity of DDR1-IN-1 in colorectal cancer cell lines.

In a BT474 human tumor xenograft model, GSK2126458 treatment results in a dose-dependent reduction in pAkt-S473 levels, and exhibits dose-dependent tumor growth inhibition at a low dose of 300 μg/kg. Besides, GSK2126458 shows low blood clearance and good oral bioavailability in four preclinical species (mouse, rat, dog, and monkey).