Challenges and opportunities for in vivo PROTAC delivery

References

• 1. Nalawansha DA, Crews CM. PROTACs: an emerging therapeutic modality in precision medicine. Cell Chem. Biol. 27(8), 998–1014 (2020).
  Medline CASGoogle Scholar
• 2. Veber DF, Johnson SR, Cheng H-Y, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 45(12), 2615–2623 (2002).
  Medline CASGoogle Scholar
• 3. Lee GT, Nagaya N, Desantis J et al. Effects of MTX-23, a novel PROTAC of androgen receptor splice variant-7 and androgen receptor, on CRPC resistant to second-line antiandrogen therapy. Mol. Cancer Ther. 20(3), 490–499 (2021).
  Medline CASGoogle Scholar
• 4. Luo G, Li Z, Lin X et al. Discovery of an orally active VHL-recruiting PROTAC that achieves robust HMGCR degradation and potent hypolipidemic activity in vivo. Acta Pharm. Sin. B 11(5), 1300–1314 (2021).
  Medline CASGoogle Scholar
• 5. Whitty A, Zhong M, Viarengo L, Beglov D, Hall DR, Vajda S. Quantifying the chameleonic properties of macrocycles and other high-molecular-weight drugs. Drug Discov. Today 21(5), 712–717 (2016).
  Medline CASGoogle Scholar
• 6. Atilaw Y, Poongavanam V, Svensson Nilsson C et al. Solution conformations shed light on PROTAC cell permeability. ACS Med. Chem. Lett. 12(1), 107–114 (2021).
  Medline CASGoogle Scholar
• 7. David L, Wenlock M, Barton P, Ritzén A. Prediction of chameleonic efficiency. ChemMedChem 16(17), 2669–2685 (2021).
  Medline CASGoogle Scholar
• 8. Ermondi G, Garcia Jimenez D, Rossi Sebastiano M, Caron G. Rational control of molecular properties is mandatory to exploit the potential of PROTACs as oral drugs. ACS Med. Chem. Lett. 12(7), 1056–1060 (2021).
  Medline CASGoogle Scholar
• 9. Hodge D, Back DJ, Gibbons S, Khoo SH, Marzolini C. Pharmacokinetics and drug–drug interactions of long-acting intramuscular cabotegravir and rilpivirine. Clin. Pharmacokinet. 60(7), 835–853 (2021).
  Medline CASGoogle Scholar
• 10. Miah AH, Smith IED, Rackham M et al. Optimization of a series of RIP2 PROTACs. J. Med. Chem. 64(17), 12978–13003 (2021).
  Medline CASGoogle Scholar