XL388 (XL-388) is a potent, selective and orally bioavailable mTOR inhibitor with IC50 of 9.9 nM.
XL388 displays no significant activity against PI3K members with IC50 of >3 uM.
XL388 inhibited cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates.
XL388 displayed good pharmacokinetics and oral exposure in multiple species with moderate bioavailability.
Oral administration of compound 28 to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity.
