Literature Highlights from April and May 2022

There’s so many interesting new publications that don’t necessarily feature key molecules, but are helpful for drug hunters to know about. Here are some other interesting reviews, technology, and targets to watch from April and May:

April 2022

  • Best Practices: Understanding PK-PD for Protein Degraders: A Review. Derek Bartlett and Adam Gilbert from Pfizer have a detailed review on understanding PK-PD for degraders, given the kinetic complexity of these molecules (e.g., bell-shaped dose responses, multistep kinetics…). They share a nice summary of experimental data to collect (e.g., protein turnover, binding rate constants) and how to build a model for a given program.
  • Technology to Watch: Screening for Non-coding RNA (ncRNA) Modulators. Jeannie Lee’s lab at HMS, in collaboration with Merck Boston scientists, found a molecule in a direct RNA-binding screen (via affinity-selection MS, ALIS) rather than in a phenotypic screen for other molecules like SMN and CD33 splicing modulators that we’ve covered before. The identified molecules seem to have phenotypic effects downstream of their RNA target (Xist). While the lead compound has a potential metal-binding element that might raise eyebrows, a control compound with the metal-binder is inactive.

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