Enabling Challenging Drug Discovery Targets Through Mass Spectrometry

Once the tractable oncology targets have been taken, what remains tends to be smooth-surfaced, disordered, or tangled in complex signaling networks, and conventional high-throughput screening struggles against them. Fei, of the Therapeutic Discovery Division at MD Anderson Cancer Center, describes how her group approaches these proteins, starting from the premise that every new modality, proximity-induced ones included, begins with a binder. The talk moves through affinity selection, covalent screening, and cell-based mass spectrometry assays, with worked examples including an allosteric site on a two-substrate enzyme and a covalent hit against a transcription factor.

Hear how the team finds starting points where structure offers little help, and what it is exploring next.