Omipalisib

Cas No.:	1086062-66-9
Chemical Name:	Omipalisib
Synonyms:	2,4-Difluoro-N-(2-methoxy-5-(4-(pyridazin-4-yl)quinolin-6-yl)pyridin-3-yl)benzenesulfonamide;2,4-Difluoro-N-[2-methoxy-5-[4-(4-pyridazinyl)-6-quinolinyl]-3-pyridinyl]benzenesulfonamide;GSK2126458 (GSK458);2,4-difluoro-N-[2-methoxy-5-(4-pyridazin-4-ylquinolin-6-yl)pyridin-3-yl]benzenesulfonamide;GSK2126458;GSK-2126458;GSK458;Omipalisib (GSK2126458, GSK458);GSK-212;Omipalisib;GSK 2126458;1X8F5A3NA0;C25H17F2N5O3S;Omipalisib [USAN:INN];2,4-difluoro-N-{2-methoxy-5-[4-(pyridazin-4-yl)quinolin;PubChem22430;Omipalisib (USAN/INN);MLS006011258
SMILES:	S(C1C([H])=C([H])C(=C([H])C=1F)F)(N([H])C1=C(N=C([H])C(=C1[H])C1C([H])=C([H])C2C(=C(C([H])=C([H])N=2)C2=C([H])N=NC([H])=C2[H])C=1[H])OC([H])([H])[H])(=O)=O
Formula:	C25H17F2N5O3S
M.Wt:	505.496
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Omipalisib (GSK2126458) is a highly selective and potent inhibitor of PI3K with Kis 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.
In Vivo:	In a BT474 human tumor xenograft model, Omipalisib (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, Omipalisib (GSK2126458) shows low blood clearance and good oral bioavailability in four preclinical species (mouse, rat, dog, and monkey)[1].
In Vitro:	Omipalisib (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. Omipalisib 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, Omipalisib (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[1]. The combination of Omipalisib or GSK1120212 with Omipalisib 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[2]. Omipalisib (GSK2126458) potentiates the antiproliferative activity of DDR1-IN-1 in colorectal cancer cell lines[3].