Cat No:LP000272
Product Name:SAR245409,Voxtalisib,XL765
CAS No:934493-76-2
Purity: ≥99%
Solubility: In DMSO
Storage: -10°C
SAR245409 (XL765) displays potent inhibitory activity against class I PI3K isoforms p110α, p110β, p110δ, and p120γ, with IC50s of 39, 110, 43, and 9 nM, respectively. The IC50 value for inhibition of PI3Kα by SAR245409 is determined at various concentrations of ATP, revealing SAR245409 to be an ATP-competitive inhibitor with an equilibrium inhibition constant (Ki) value of 13 nM. SAR245409 also inhibits mTOR (IC50s of 160 and 910 nM for mTORC1 and mTORC2, respectively) in an immune-complex kinase assay and the PI3K-related kinase DNA-PK (IC50 value of 150 nM). In contrast, SAR245409 has relatively weak inhibitory activity toward the class III PI3K vacuolar sorting protein 34 (VPS34; IC50 value of ~9.1 μM). Consistent with its inhibitory activity against purified PI3K proteins, SAR245409 inhibits EGF-induced PIP3 production in PC-3 and MCF7 cells with IC50s of 290 and 170 nM, respectively. The ability of SAR245409 to inhibit phosphorylation of key signaling proteins downstream of PI3K is examined by assessing its effects on EGF-stimulated phosphorylation of AKT and on nonstimulated phosphorylation of S6 in PC-3 cells by cell-based ELISA. SAR245409 inhibits these activities with IC50s of 250 and 120 nM, respectively. In MCF7 and PC-3 cells, SAR245409 inhibits proliferation (monitored by BrdUrd incorporation) with IC50s of 1,070 and 1,840 nM, respectively. To further characterize the effects of SAR245409 on tumor cell growth, an assay monitoring the anchorage-independent growth of PC-3 and MCF7 cells in soft agar over a 14-day period is used. SAR245409 inhibits colony growth with an IC50 value of 270 nM in PC-3 cells and 230 nM in MCF7 cells
