GSK2126458 (GSK458)

Name	2,4-difluoro-N-(2-methoxy-5-(4-(pyridazin-4-yl)quinolin-6-yl)pyridin-3-yl)benzenesulfonamide
Synonyms	CS-55 HYR-582 GSK2126458 GSK-2126458 GSK-2126458 GSK2126458 (GSK458) Omipalisib GSK2126458 BML-275 2HCL,COMPOUND C 2HCL GSK2126458 (HYR-582) 2,4-Difluoro-N-[2-methoxy-5-[4-(4-pyridazinyl)-6-quinolinyl]-3-pyridinyl]benzenesulfonamide 2,4-difluoro-N-(2-methoxy-5-(4-(pyridazin-4-yl)quinolin-6-yl)pyridin-3-yl)benzenesulfonamide
CAS	1086062-66-9
EINECS	629-873-1

Molecular Formula	C25H17F2N5O3S
Molar Mass	505.5
Density	1.45
Melting Point	187-189℃
Boling Point	715.6±70.0 °C(Predicted)
Solubility	Soluble in DMSO, not in water
Appearance	Solid
Color	White to Pale Yellow
pKa	6.23±0.40(Predicted)
Storage Condition	Refrigerator
Use	Omipalisib (GSK2126458) is an orally effective, highly selective PI3K inhibitor that inhibits the activity of p110α/β/δ/γ,mTORC1/2 with Ki values of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM, respectively.
In vitro study	GSK2126458 potently inhibits the common activating mutant of p110α(E542K, e5445k, and H1047R) found in human cancer cells with Ki of 8 pM, 8 pM, and 9 pM, respectively. GSK2126458 significantly reduced the level of T47D and BT474 cells by pAKT-S473, with IC50 of 0.41 nM and 0.18 nM, respectively. Furthermore, GSK2126458 acts on a variety of cell lines, including the T47D and BT474 breast cancer cell lines, causing the cell cycle to stop at G1 phase and inhibiting cell proliferation with IC50 of 3 nM and 2.4 nM, respectively.
In vivo study	The effect of GSK2126458 on BT474 human xenograft tumor model was reduced by pAKT-S473, which was dose-dependent, and the effect was inhibited by 300 μg /kg low dose. In addition, GSK2126458 acts on four preclinical species (mouse, rat, dog, and monkey) with low blood clearance and good oral bioavailability.