Genentech

Unraveling Unexpected Palladium Catalyst Poisoning by Liquid Chromatography–Mass Spectrometry

Abstract Palladium-catalyzed cross-coupling reactions are cornerstones of drug manufacturing during pharmaceutical development. However, their efficiencies can be susceptible to trace levels of “catalyst poisons”, particularly at low palladium loadings. These poisons decimate rea...

Harnessing Quantitative Medicine to Advance Oncology Drug Development

Oncology drug development continues to have a high attrition rate despite major advances in therapeutic modalities such as antibody-drug conjugates, bispecific antibodies, cell therapies, and cancer vaccines. Critical development decisions are often made under substantial uncerta...

Synthesis of the pan-TEAD Inhibitor GDC-8025 via a Flow Chan–Evans–Lam Coupling and Enantioselective Biocatalytic α-Ketoester Reduction

Abstract GDC-8025 is a potent pan-TEAD inhibitor that features a functionalized 1H-pyrazolo[3,4-b]pyridine core and a reactive acrylamide warhead. The first-generation synthesis of GDC-8025 relied on a Sharpless asymmetric dihydroxylation of 7 to install the chiral diol moiety (8...