Tsai, J. M., Nowak, R. P., Ebert, B. L. & Fischer, E. S. Focused protein degradation: from mechanisms to clinic. Nat. Rev. Mol. Cell Biol. 25, 740–757 (2024). This evaluation systematically examined TPD mechanisms and positioned particular emphasis on their progress in the direction of scientific translation.
Garber, Okay. The PROTAC gold rush. Nat. Biotechnol. 40, 12–16 (2022). This commentary captured the joy round PROTACs, noting their promise for‘undruggable’ targets and likewise the uncertainties of scientific success.
Békés, M., Langley, D. R. & Crews, C. M. PROTAC focused protein degraders: the previous is prologue. Nat. Rev. Drug Discov. 21, 181–200 (2022). This paper comprehensively traced the rise of PROTACs and summarized the important thing milestones that formed the sector.
Baek, Okay. & Schulman, B. A. Molecular glue idea solidifies. Nat. Chem. Biol. 16, 2–3 (2020).
Yoon, H., Rutter, J. C., Li, Y.-D. & Ebert, B. L. Induced protein degradation for therapeutics: previous, current, and future. J. Clin. Make investments. 134, e175265 (2024).
Ge, J. et al. PROTAC-DB 3.0: an up to date database of PROTACs with prolonged pharmacokinetic parameters. Nucleic Acids Res. 53, D1510–D1515 (2024).
Hsia, O. et al. Focused protein degradation by way of intramolecular bivalent glues. Nature 627, 204–211 (2024).
Liu, Y. et al. Increasing PROTACtable genome universe of E3 ligases. Nat. Commun. 14, 6509 (2023).
Guenette, R. G., Yang, S. W., Min, J., Pei, B. & Potts, P. R. Goal and tissue selectivity of PROTAC degraders. Chem. Soc. Rev. 51, 5740–5756 (2022).
Campone, M. et al. Vepdegestrant, a PROTAC estrogen receptor degrader, in superior breast most cancers. N. Engl. J. Med. 393, 556–568 (2025). This paper summarized the Section 3 scientific trial outcomes of the pioneering PROTAC ARV-471, demonstrating optimistic advantages in sure subpopulations and highlighting the necessity for personalised drugs.
Li, Z. et al. Allele-selective decreasing of mutant HTT protein by HTT–LC3 linker compounds. Nature 575, 203–209 (2019). This research is an early instance of utilizing high-throughput screening to find small molecules that direct mutant huntingtin to autophagosomes for degradation.
Takahashi, D. et al. AUTACs: cargo-specific degraders utilizing selective autophagy. Mol. Cell 76, 797–810.e710 (2019).
Ji, C. H. et al. The AUTOTAC chemical biology platform for focused protein degradation by way of the autophagy-lysosome system. Nat. Commun. 13, 904 (2022).
Bence, N. F., Sampat, R. M. & Kopito, R. R. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292, 1552–1555 (2001).
Muhar, M. F. et al. C-terminal amides mark proteins for degradation by way of SCF–FBXO31. Nature 638, 519–527 (2025).
Wang, D. et al. Mitochondrial protease focusing on chimeras for mitochondrial matrix protein degradation. J. Am. Chem. Soc. 145, 12861–12869 (2023).
Liu, C. X. et al. An endoplasmic reticulum (ER)-targeting DNA nanodevice for autophagy-dependent degradation of proteins in membrane-bound organelles. Angew. Chem. Int. Ed. 61, e202205509 (2022).
Lu, P. et al. Selective degradation of multimeric proteins by TRIM21-based molecular glue and PROTAC degraders. Cell 187, 7126–7142.e7120 (2024).
Gu, X. et al. The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation. Science 381, eadh5021 (2023).
Lascaux, P. et al. TEX264 drives selective autophagy of DNA lesions to advertise DNA restore and cell survival. Cell 187, 5698–5718.e5626 (2024).
Liu, H. et al. TFAM is an autophagy receptor that limits irritation by binding to cytoplasmic mitochondrial DNA. Nat. Cell Biol. 26, 878–891 (2024).
Chen, Y. et al. Rpl12 is a conserved ribophagy receptor. Nat. Cell Biol. 27, 477–492 (2025).
Koutsifeli, P. et al. Glycogen-autophagy: molecular equipment and mobile mechanisms of glycophagy. J. Biol. Chem. 298, 102093 (2022).
Zhang, J. et al. Single amino acid primarily based PROTACs set off degradation of the oncogenic kinase ABL in continual myeloid leukemia (CML). J. Biol. Chem. 299, 104994 (2023).
Zhang, S. et al. The regulation, perform, and function of lipophagy, a type of selective autophagy, in metabolic issues. Cell Dying Dis. 13, 132 (2022).
Jung, H. et al. Anti-inflammatory clearance of amyloid-β by a chimeric Gas6 fusion protein. Nat. Med. 28, 1802–1812 (2022).
Uhlén, M. et al. Tissue-based map of the human proteome. Science 347, 1260419 (2015).
Banik, S. M. et al. Lysosome-targeting chimaeras for degradation of extracellular proteins. Nature 584, 291–297 (2020). This research pioneered lysosome-targeting chimeras for extracellular protein degradation, inspiring additional analysis.
Ahn, G. et al. Elucidating the mobile determinants of focused membrane protein degradation by lysosome-targeting chimeras. Science 382, eadf6249 (2023).
Wells, J. A. & Kumru, Okay. Extracellular focused protein degradation: an rising modality for drug discovery. Nat. Rev. Drug Discov. 23, 126–140 (2024).
Zhang, D. et al. Transferrin receptor focusing on chimeras for membrane protein degradation. Nature 638, 787–795 (2025).
Liu, Y. et al. Focused protein degradation by way of mobile trafficking of nanoparticles. Nat. Nanotechnol. 20, 296–302 (2025). This research comprehensively demonstrates that ligand-installed nanoparticles can degrade their corresponding membrane proteins throughout various nanoparticle formulations and ligand varieties.
Huang, X. et al. Nanoreceptors promote mutant p53 protein degradation by mimicking selective autophagy receptors. Nat. Nanotechnol. 19, 545–553 (2024). This research pioneers using ligand-installed nanoparticles to degrade the intracellular protein mutant p53 and demonstrates that nanoparticle optimistic cost enhances their degradation capability.
Yao, S. et al. A plug-and-play monofunctional platform for focused degradation of extracellular proteins and vesicles. Nat. Commun. 15, 7237 (2024).
Qi, J. et al. Semiconducting polymer nanoparticles with surface-mimicking protein secondary construction as lysosome-targeting chimaeras for self-synergistic most cancers immunotherapy. Adv. Mater. 34, 2203309 (2022).
Wang, X. et al. Lysosome-targeting protein degradation by way of endocytosis pathway triggered by polyvalent nano-chimera for AD remedy. Adv. Mater. 37, 2411061 (2025).
Fan, Okay. et al. Bioengineered ferritin-based LYTAC platform for tumor-targeted remedy. Preprint at Analysis Sq. https://doi.org/10.21203/rs.3.rs-5515153/v1 (2025).
Jin, P. et al. Improvement of a nano-targeting chimera for the degradation of membrane and cytoplasmic proteins. Acta Biomater. 195, 509–521 (2025).
Mukhopadhyay, A., Basu, S., Singha, S. & Patra, H. Okay. Interior-view of nanomaterial incited protein conformational adjustments: insights into designable interplay. Analysis 2018, 9712832 (2018).
Track, Y., Cui, L., Liu, Z., Tang, Z. & Chen, X. Multivalent RGD peptide-mediated nanochimera for lysosomal degradation of PDL1 orotein. Nano Lett. 25, 4078–4086 (2025).
Cheng, Q. et al. Selective organ focusing on (SORT) nanoparticles for tissue-specific mRNA supply and CRISPR–Cas gene modifying. Nat. Nanotechnol. 15, 313–320 (2020).
Dilliard, S. A., Cheng, Q. & Siegwart, D. J. On the mechanism of tissue-specific mRNA supply by selective organ focusing on nanoparticles. Proc. Natl Acad. Sci. USA 118, e2109256118 (2021).
Wang, S. et al. The function of protein corona on nanodrugs for organ-targeting and its prospects of software. J. Management. Launch 360, 15–43 (2023).
Qiu, C. et al. Superior methods for overcoming endosomal/lysosomal barrier in nanodrug supply. Analysis 6, 0148 (2023).
McNally, Okay. E. & Cullen, P. J. Endosomal retrieval of cargo: retromer is just not alone. Tendencies Cell Biol. 28, 807–822 (2018).
Akinc, A. et al. The Onpattro story and the scientific translation of nanomedicines containing nucleic acid-based medicine. Nat. Nanotechnol. 14, 1084–1087 (2019).
Nguyen, L. N. M. et al. The mechanisms of nanoparticle supply to stable tumours. Nat. Rev. Bioeng. 2, 201–213 (2024).
Nguyen, L. N. et al. The exit of nanoparticles from stable tumours. Nat. Mater. 22, 1261–1272 (2023).
Sindhwani, S. et al. The entry of nanoparticles into stable tumours. Nat. Mater. 19, 566–575 (2020).
Cabral, H., Li, J., Miyata, Okay. & Kataoka, Okay. Controlling the biodistribution and clearance of nanomedicines. Nat. Rev. Bioeng. 2, 214–232 (2024).
Mi, P., Cabral, H. & Kataoka, Okay. Ligand-installed nanocarriers towards precision remedy. Adv. Mater. 32, 1902604 (2020).
Zheng, S. et al. Accelerated rational PROTAC design by way of deep studying and molecular simulations. Nat. Mach. Intell. 4, 739–748 (2022).
Chen, D., Liu, J. & Wei, G.-W. Multiscale topology-enabled structure-to-sequence transformer for protein–ligand interplay predictions. Nat. Mach. Intell. 6, 799–810 (2024).
Adir, O. et al. Integrating synthetic intelligence and nanotechnology for precision most cancers drugs. Adv. Mater. 32, 1901989 (2020).
Rao, L., Yuan, Y., Shen, X., Yu, G. & Chen, X. Designing nanotheranostics with machine studying. Nat. Nanotechnol. 19, 1769–1781 (2024).