Douglas A. Whittington

TL;DR: AMG 176 is a potent, selective, and orally bioavailable MCL1 inhibitor that induces a rapid commitment to apoptosis in models of hematologic malignancies and the synergistic combination of AMG 176 and venetoclax is synergistic in acute myeloid leukemia (AML) tumor models and in primary patient samples at tolerated doses.

TL;DR: Structural-based design efforts leading to the identification of a novel quinazolinone scaffold are described, along with optimization efforts that overcame a configurational stability issue arising from restricted rotation about an axially chiral biaryl bond, and biopharmaceutical optimization of the resulting leads culminated in AMG 510.

TL;DR: The synthesis and structure-activity relationship of a series of 2-aminobenzimidazoles and benzoxazoles are described, culminating in the identification of Benzoxazole 22 as a potent and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile.

TL;DR: This work reports the discovery of compound 82 as a potent dual inhibitor of PI3K and mTOR, which exhibited potent enzyme and cell activity, low clearance, and high oral bioavailability and demonstrated tumor growth inhibition in U-87 MG, A549, and HCT116 tumor xenograft models.