4,031
Views
0
CrossRef citations to date
0
Altmetric
Editorial

Investigating the cell permeability of proteolysis-targeting chimeras (PROTACs)

ORCID Icon, ORCID Icon & ORCID Icon
Pages 357-361 | Received 13 Jan 2023, Accepted 28 Feb 2023, Published online: 12 Mar 2023

References

  • Cecchini C, Tardy S, Scapozza L. Linkers as game-changers in protac technology: emphasizing general trends in PROTAC pharmacokinetics for their rational design. Chimica. 2022;76(4):341–345.
  • Lipinski CA, Lombardo F, Dominy BW, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1–3):3–26.
  • Veber DF, Johnson SR, Cheng HY, et al. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45(12):2615–2623.
  • Klein VG, Bond AG, Craigon C, et al. Amide-to-ester substitution as a strategy for optimizing PROTAC permeability and cellular activity. J Med Chem. 2021;64(24):18082–18101.
  • Kerns EH, Di L, Carter GT. In vitro solubility assays in drug discovery. Curr Drug Metab. 2008;9(9):879–885.
  • Jimenez DG, Sebastiano MR, Caron G, et al. Are we ready to design oral PROTACs®? ADMET DMPK. 2021;9(4):243–254.
  • Scott DE, Rooney TPC, Bayle ED, et al. Systematic investigation of the permeability of androgen receptor PROTACs. ACS Med Chem Lett. 2020;11(8):1539–1547.
  • Galdeano C, Gadd MS, Soares P, et al. Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von Hippel–Lindau (VHL) E3 ubiquitin ligase and the Hypoxia Inducible Factor (HIF) alpha subunit with in vitro nanomolar affinities. J Med Chem. 2014;57(20):8657–8663.
  • Lv D, Pal P, Liu X, et al. Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity. Nat Commun. 2021;12(1):6896.
  • Maple HJ, Clayden N, Baron A, et al. Developing degraders: principles and perspectives on design and chemical space. MedChemComm. 2019;10(10):1755–1764.
  • Yokoo H, Shibata N, Endo A, et al. Discovery of a highly potent and selective degrader targeting hematopoietic prostaglandin D synthase via in silico design. J Med Chem. 2021;64(21):15868–15882.
  • Poongavanam V, Atilaw Y, Siegel S, et al. Linker-dependent folding rationalizes PROTAC cell permeability. J Med Chem. 2022;65(19):13029–13040.
  • Lebraud H, Wright DJ, Johnson CN, et al. Protein degradation by in-cell self-assembly of proteolysis targeting chimeras. ACS Cent Sci. 2016;2(12):927–934.
  • Wei M, Zhao R, Cao Y, et al. First orally bioavailable prodrug of proteolysis targeting chimera (PROTAC) degrades cyclin-dependent kinases 2/4/6 in vivo. Eur J Med Chem. 2021;209:112903.
  • Liu J, Chen H, Liu Y, et al. Cancer selective target degradation by folate-caged PROTACs. J Am Chem Soc. 2021;143(19):7380–7387.
  • Dragovich PS, Pillow TH, Blake RA, et al. Antibody-mediated delivery of chimeric BRD4 degraders. part 1: exploration of antibody linker, payload loading, and payload molecular properties. J Med Chem. 2021;64(5):2534–2575.
  • He S, Gao F, Ma J, et al. Aptamer-PROTAC conjugates (APCS) for tumor-specific targeting in breast cancer. Angew Chem Int Ed. 2021;60(43):23299–23305.
  • Sakamoto KM, Kim KB, Kumagai A, et al. Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. Proc Natl Acad Sci USA. 2001;98(15):8554–8559.
  • Yokoo H, Ohoka N, Takyo M, et al. Peptide stapling improves the sustainability of a peptide-based chimeric molecule that induces targeted protein degradation. Int J Mol Sci. 2021;22(16):8772.
  • Chen Y, Tandon I, Heelan W, et al. Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation. Chem Soc Rev. 2022;51(13):5330–5350.
  • Zhang C, Zeng Z, Cui D, et al. Semiconducting polymer nano-PROTACs for activatable photo-immunometabolic cancer therapy. Nat Commun. 2021;12(1):2934.
  • Pike A, Williamson B, Harlfinger S, et al. Optimising proteolysis-targeting chimeras (PROTACs) for oral drug delivery: a drug metabolism and pharmacokinetics perspective. Drug Discov Today. 2020;25(10):1793–1800.
  • Hendrick CE, Jorgensen JR, Chaudhry C, et al. Direct-to-biology accelerates PROTAC synthesis and the evaluation of linker effects on permeability and degradation. ACS Med Chem Lett. 2022;13(7):1182–1190.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.