The landscape of small-molecule prodrugs

Rautio, J., Meanwell, N. A., Di, L. & Hageman, M. J. The expanding role of prodrugs in contemporary drug design and development. Nat. Rev. Drug Discov. 17, 559–587 (2018).

Article  CAS  PubMed  Google Scholar 

Mitchell, M. J. et al. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 20, 101–124 (2021).

Article  CAS  PubMed  Google Scholar 

Narang, A. S. & Boddu, S. H. S. in Excipient Applications in Formulation Design and Drug Delivery (eds Narang, A. S. & Boddu, S. H. S) 1–10 (Springer, 2015).

Zhao, Z., Ukidve, A., Kim, J. & Mitragotri, S. Targeting strategies for tissue-specific drug delivery. Cell 181, 151–167 (2020).

Article  CAS  PubMed  Google Scholar 

Elsharkasy, O. M. et al. Extracellular vesicles as drug delivery systems: why and how? Adv. Drug Deliv. Rev. 159, 332–343 (2020).

Article  CAS  PubMed  Google Scholar 

Huttunen, K. M., Raunio, H. & Rautio, J. Prodrugs—from serendipity to rational design. Pharmacol. Rev. 63, 750–771 (2011).

Article  CAS  PubMed  Google Scholar 

Najjar, A. & Karaman, R. The prodrug approach in the era of drug design. Expert Opin. Drug. Deliv. 16, 1–5 (2018).

Article  PubMed  Google Scholar 

Jordheim, L. P., Durantel, D., Zoulim, F. & Dumontet, C. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat. Rev. Drug Discov. 12, 447–464 (2013).

Article  CAS  PubMed  Google Scholar 

Wang, Y. et al. Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics. Nucleic Acids Res. 48, D1031–D1041 (2020).

CAS  PubMed  Google Scholar 

Degtyarenko, K. et al. ChEBI: a database and ontology for chemical entities of biological interest. Nucleic Acids Res. 36, D344–D350 (2007).

Article  PubMed  PubMed Central  Google Scholar 

Mullard, A. 2022 FDA approvals. Nat. Rev. Drug Discov. 22, 83–88 (2023).

Article  CAS  PubMed  Google Scholar 

Mullard, A. 2021 FDA approvals. Nat. Rev. Drug Discov. 21, 83–98 (2022).

Article  CAS  PubMed  Google Scholar 

Mullard, A. 2020 FDA drug approvals. Nat. Rev. Drug Discov. 20, 85–91 (2021).

Article  CAS  PubMed  Google Scholar 

Mullard, A. 2019 FDA drug approvals. Nat. Rev. Drug Discov. 19, 79–84 (2020).

Article  CAS  PubMed  Google Scholar 

Wishart, D. S. et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 46, D1074–D1082 (2018).

Article  CAS  PubMed  Google Scholar 

Zhou, Y. et al. Therapeutic target database update 2022: facilitating drug discovery with enriched comparative data of targeted agents. Nucleic Acids Res. 50, D1398–D1407 (2022).

Article  CAS  PubMed  Google Scholar 

Sugawara, M. et al. Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J. Pharm. Sci. 89, 781–789 (2000).

Article  CAS  PubMed  Google Scholar 

Peppercorn, M. A. Sulfasalazine: pharmacology, clinical use, toxicity, and related new drug development. Ann. Intern. Med. 101, 377–386 (1984).

Article  CAS  PubMed  Google Scholar 

Asaki, T. et al. Selexipag: an oral and selective IP prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. J. Med. Chem. 58, 7128–7137 (2015).

Article  CAS  PubMed  Google Scholar 

Lee, W. A. & Cheng, A. K. Tenofovir alafenamide fumarate. Antivir. Ther. 27, 13596535211067600 (2022).

Article  CAS  PubMed  Google Scholar 

Jankovic, J. Dopamine depleters in the treatment of hyperkinetic movement disorders. Expert Opin. Pharmacother. 17, 2461–2470 (2016).

Article  CAS  PubMed  Google Scholar 

Reigner, B., Blesch, K. & Weidekamm, E. Clinical pharmacokinetics of capecitabine. Clin. Pharmacokinet. 40, 85–104 (2001).

Article  CAS  PubMed  Google Scholar 

Aljuffali, I. A., Lin, C.-F., Chen, C.-H. & Fang, J.-Y. The codrug approach for facilitating drug delivery and bioactivity. Expert Opin. Drug Deliv. 13, 1311–1325 (2016).

Article  CAS  PubMed  Google Scholar 

Friedel, H. A., Campoli-Richards, D. M. & Goa, K. L. Sultamicillin. Drugs 37, 491–522 (1989).

Article  CAS  PubMed  Google Scholar 

Mueller, C. E. Prodrug approaches for enhancing the bioavailability of drugs with low solubility. Chem. Biodivers. 6, 2071–2083 (2009).

Article  CAS  Google Scholar 

Barlow, N., Chalmers, D. K., Williams-Noonan, B. J., Thompson, P. E. & Norton, R. S. Improving membrane permeation in the beyond rule-of-five space by using prodrugs to mask hydrogen bond donors. ACS Chem. Biol. 15, 2070–2078 (2020).

Article  CAS  PubMed  Google Scholar 

Murakami, T. A minireview: usefulness of transporter-targeted prodrugs in enhancing membrane permeability. J. Pharm. Sci. 105, 2515–2526 (2016).

Article  CAS  PubMed  Google Scholar 

Camp, D., Garavelas, A. & Campitelli, M. Analysis of physicochemical properties for drugs of natural origin. J. Nat. Prod. 78, 1370–1382 (2015).

Article  CAS  PubMed  Google Scholar 

Hall, B. S. & Wilkinson, S. R. Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation. Antimicrob. Agents Chemother. 56, 115–123 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jubeh, B., Breijyeh, Z. & Karaman, R. Antibacterial prodrugs to overcome bacterial resistance. Molecules 25, 1543 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin, D. et al. Bacterial-based cancer therapy: an emerging toolbox for targeted drug/gene delivery. Biomaterials 277, 121124 (2021).

Article  CAS  PubMed  Google Scholar 

Li, Y., Zhao, L. & Li, X.-F. Targeting hypoxia: hypoxia-activated prodrugs in cancer therapy. Front. Oncol. 11, 700407 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Peiró Cadahía, J., Previtali, V., Troelsen, N. S. & Clausen, M. H. Prodrug strategies for targeted therapy triggered by reactive oxygen species. Medchemcomm 10, 1531–1549 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Padilla, A. M. et al. Discovery of an orally active benzoxaborole prodrug effective in the treatment of Chagas disease in non-human primates. Nat. Microbiol. 7, 1536–1546 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cundy, K. C. et al. XP13512 [(±)-1-([(α-Isobutanoyloxyethoxy) carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: I. Design, synthesis, enzymatic conversion to gabapentin, and transport by intestinal solute transporters. J. Pharmacol. Exp. Ther. 311, 315–323 (2004).

Article  CAS  PubMed  Google Scholar 

Salem, A. H. et al. Expanding the repertoire for “Large small molecules”: prodrug abbv-167 efficiently converts to venetoclax with reduced food effect in healthy volunteers. Mol. Cancer Ther. 20, 999–1008 (2021).

Article  CAS  PubMed  Google Scholar 

Halpern, L. The transfer of inorganic phosphorus across the red blood cell membrane. J. Biol. Chem. 114, 747–770 (1936).

Article  CAS  Google Scholar 

Wiemer, A. J. Metabolic efficacy of phosphate prodrugs and the remdesivir paradigm. ACS Pharmacol. Transl. Sci. 3, 613–626 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ohwada, J. et al. Design, synthesis and antifungal activity of a novel water soluble prodrug of antifungal triazole. Bioorg. Med. Chem. Lett. 13, 191–196 (2003).

Article  CAS 

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