1-(4-{[4-(dimethylamino)piperidin-1-yl]carbonyl}phenyl)-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea (PKI-587, PF-05212384)

OTAVAchemicals Catalogue Number:  7070707142

CAS Registry Number:  1197160-78-3

Purity:  95%+

Ref.: Venkatesan et al. Bis(morpholino-1,3,5-triazine) Derivatives: Potent Adenosine 5′-Triphosphate Competitive Phosphatidylinositol-3-kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of Compound 26 (PKI-587), a Highly Efficacious Dual Inhibitor. Journal of Medicinal Chemistry (2010), 53, 2636-2645

Abstract: The PI3K/Akt signaling pathway is a key pathway in cell proliferation, growth, survival, protein synthesis,and glucose metabolism. It has been recognized recently that inhibiting this pathway might provide a viabletherapy for cancer. A series of bis(morpholino-1,3,5-triazine) derivatives were prepared and optimized to provide the highly efficacious PI3K/mTOR inhibitor 1-(4-{[4-(dimethylamino)piperidin-1-yl]car-bonyl}phenyl)-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea 26 (PKI-587). Compound 26 has shown excellent activity in vitro and in vivo, with antitumor efficacy in both subcutaneous and orthotopic xenograft tumor models when administered intravenously. The structure-activity relationships and the invitro and in vivo activity of analogues in this series are described.