Add time:07/13/2019 Source:sciencedirect.com
Recently, the phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) have been considered as promising targets for the treatment of cancer. Herein, we synthesized a series of N-(5-(quinolin-6-yl)pyridin-3-yl)benzenesulfonamides as novel PI3K/mTOR dual inhibitors for cancer therapy. In the biological evaluation, compound 17e was identified as a potent PI3K/mTOR dual inhibitor, which significantly inhibit Class I PI3Ks, mTOR and phosphorylation of pAkt(Ser473) at low nanomolar level. Moreover, 17e display high potency against PC-3 cells (IC50 = 80 nM) in the anti-proliferative assay, and showed acceptable pharmacokinetic properties in vivo.
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