Samantha J. Richardson

TL;DR: Replacing liver microsome and hepatocyte assays with S9 assay for high throughput metabolic screening purposes provides the combined benefit of comprehensive and high quality data at a reasonable expense for drug discovery programs.

TL;DR: SAR studies examining the potency, selectivity, and PK parameters for a series of triazole containing 4,6- or 1,7-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones resulted in the identification of triAZole containing mTOR kinase inhibitors with improved PK properties.

TL;DR: CC-223 is a potent, selective, and orally bioavailable inhibitor of mTOR kinase, demonstrating inhibition of m TORC1 (pS6RP and p4EBP1) and mTORC2 [pAKT(S473)] in cellular systems, and is currently in phase I clinical trials.

TL;DR: The synthesis and structure-activity relationship (SAR) of a novel series of mammalian target of rapamycin kinase inhibitors, with exquisite kinase selectivity over the related lipid kinase PI3K is reported.

TL;DR: Wide range in in vitro and in vivo ADME data makes these particular ADME assays non-discriminatory in the selection of promising compounds, and non-traditional assays such as target mass modification, target confirmation by amino acid sequencing, cellular target occupancy, and target turnover rate data are the critical considerations for progression of irreversible compounds in early discovery.