Proteolysis targeting chimeras (PROTACs) in 'beyond rule-of-five' chemical space: Recent progress and future challenges

  • Bioorg Med Chem Lett. 2019 Jul 1;29(13):1555-1564. doi: 10.1016/j.bmcl.2019.04.030.
Scott D Edmondson  1 ,  Bin Yang  2 ,  Charlene Fallan  3
Affiliations
  • 1. Medicinal Chemistry, Oncology, IMED Biotech Unit, AstraZeneca, Boston, MA, USA. Electronic address: [email protected].
  • 2. Medicinal Chemistry, Oncology, IMED Biotech Unit, AstraZeneca, Boston, MA, USA.
  • 3. Medicinal Chemistry, Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, UK.
PMID: 31047748 DOI: 10.1016/j.bmcl.2019.04.030
Abstract

Proteolysis targeting chimeras (PROTACs) are heterobifunctional compounds with molecular weights and Other properties that lie outside the classic 'rule-of-five' space. Consequently, PROTACs have unique challenges associated with their development as potential therapeutic agents. This review summarizes and analyzes a representative set of recent PROTACs and highlights some of the potential future challenges facing this promising modality.

Keywords
Absorption; Beyond rule-of-five; Degradation; Oral bioavailability; PROTACs; Proteolysis targeting chimeras; bRo5.