Phosphoinositide 3-kinase (PI3K) dependent signaling is frequently activated in human cancers. Herein, we describe our efforts to develop PI3K inhibitors as potential cancer therapeutics. Optimization of pyridyltriazine 1 led to clinical candidate AMG 511 (Figure 1), a potent pan inhibitor of class I PI3Ks with a superior pharmacokinetic profile. AMG 511 was shown to potently block the targeted PI3K pathway in a mouse liver pharmacodynamic model and inhibit tumor growth in a U87 xenograft model. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/coil4/uploads/87544_figure_1.jpg' alt='' />

Identification of AMG 511 as a selective class I phosphoinositide 3-kinase inhibitor

245th National Meeting (2013)

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