体外研究
Acalisib (GS-9820) is more selective for PI3Kδ (IC 50 =12.7 nM) relative to other PI3K class I enzymes (IC 50 : PI3Kα, 5,441 nM; PI3Kβ, 3,377 nM; PI3Kγ, 1,389 nM). Acalisib is also 10 3 -fold more selective against PI3Kδ than against related kinases, such as PI3KCIIβ (IC 50 >10 nM), hVPS34 (IC 50 =12.7 μM), DNA-PK (IC 50 =18.7 μM), and mTOR (IC 50 >10 nM). In fibroblasts, the PDGF receptor signals through PI3Kα and the GPCR for lysophosphatidic acid (LPA) signals through PI3Kβ. Acalisib reduces PDGF-induced pAkt by only 50% at 11,585 nM, and LPA-induced pAkt by 50% at 2,069 nM.
编辑结构
