Chirnomas D, Hornberger KR, Crews CM (2023) Protein degraders enter the clinic - a new approach to cancer therapy. Nat Rev Clin Oncol 20:265–278. https://doi.org/10.1038/s41571-023-00736-3

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xie X, Yu T, Li X et al (2023) Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials. Signal Transduct Target Ther 8:335. https://doi.org/10.1038/s41392-023-01589-z

Article  PubMed  PubMed Central  Google Scholar 

Dragovich PS (2022) Degrader-antibody conjugates. Chem Soc Rev 51:3886–3897. https://doi.org/10.1039/d2cs00141a

Article  CAS  PubMed  Google Scholar 

Nguyen TD, Bordeau BM, Balthasar JP (2023) Mechanisms of ADC toxicity and strategies to increase ADC tolerability. Cancers (Basel) 15:713. https://doi.org/10.3390/cancers15030713

Article  CAS  PubMed  Google Scholar 

Conilh L, Sadilkova L, Viricel W, Dumontet C (2023) Payload diversification: a key step in the development of antibody-drug conjugates. J Hematol Oncol 16:3. https://doi.org/10.1186/s13045-022-01397-y

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bondeson DP, Mares A, Smith IED et al (2015) Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat Chem Biol 11:611–617. https://doi.org/10.1038/nchembio.1858

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dragovich PS, Pillow TH, Blake RA et al (2021) Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 1: Exploration of Antibody Linker, Payload Loading, and Payload Molecular Properties. J Med Chem 64:2534–2575. https://doi.org/10.1021/acs.jmedchem.0c01845

Article  CAS  PubMed  Google Scholar 

Dragovich PS, Pillow TH, Blake RA et al (2021) Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 2: Improvement of In Vitro Antiproliferation Activity and In Vivo Antitumor Efficacy. J Med Chem 64:2576–2607. https://doi.org/10.1021/acs.jmedchem.0c01846

Article  CAS  PubMed  Google Scholar 

Bartlett DW, Gilbert AM (2021) A kinetic proofreading model for bispecific protein degraders. J Pharmacokinet Pharmacodyn 48:149–163. https://doi.org/10.1007/s10928-020-09722-z

Article  CAS  PubMed  Google Scholar 

Bartlett DW, Gilbert AM (2022) Translational PK-PD for targeted protein degradation. Chem Soc Rev 51:3477–3486. https://doi.org/10.1039/d2cs00114d

Article  CAS  PubMed  Google Scholar 

Shah DK, Haddish-Berhane N, Betts A (2012) Bench to bedside translation of antibody drug conjugates using a multiscale mechanistic PK/PD model: a case study with brentuximab-vedotin. J Pharmacokinet Pharmacodyn 39:643–659. https://doi.org/10.1007/s10928-012-9276-y

Article  PubMed  Google Scholar 

Yamazaki S, Nguyen L, Vekich S et al (2011) Pharmacokinetic-pharmacodynamic modeling of biomarker response and tumor growth inhibition to an orally available heat shock protein 90 inhibitor in a human tumor xenograft mouse model. J Pharmacol Exp Ther 338:964–973. https://doi.org/10.1124/jpet.111.181339

Article  CAS  PubMed  Google Scholar 

Mager DE, Jusko WJ (2001) Pharmacodynamic modeling of time-dependent transduction systems. Clin Pharmacol Ther 70:210–216. https://doi.org/10.1067/mcp.2001.118244

Article  CAS  PubMed  Google Scholar 

Lobo ED, Balthasar JP (2002) Pharmacodynamic modeling of chemotherapeutic effects: application of a transit compartment model to characterize methotrexate effects in vitro. AAPS PharmSci 4:E42. https://doi.org/10.1208/ps040442

Article  PubMed  Google Scholar 

Maneiro MA, Forte N, Shchepinova MM et al (2020) Antibody-PROTAC conjugates enable HER2-dependent targeted protein degradation of BRD4. ACS Chem Biol 15:1306–1312. https://doi.org/10.1021/acschembio.0c00285

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang A, Seiss K, Laborde L et al (2024) Design, synthesis, and in vitro and in vivo evaluation of cereblon binding Bruton’s tyrosine kinase (BTK) degrader CD79b targeted antibody-drug conjugates. Bioconjug Chem 35:140–146. https://doi.org/10.1021/acs.bioconjchem.3c00535

Article  CAS  PubMed  Google Scholar 

Pillow TH, Adhikari P, Blake RA et al (2020) Antibody conjugation of a chimeric BET degrader enables in vivo activity. ChemMedChem 15:17–25. https://doi.org/10.1002/cmdc.201900497

Article  CAS  PubMed  Google Scholar 

An S, Fu L (2018) Small-molecule protacs: an emerging and promising approach for the development of targeted therapy drugs. EBioMedicine 36:553–562. https://doi.org/10.1016/j.ebiom.2018.09.005

Article  PubMed  PubMed Central  Google Scholar 

Hamblett KJ, Jacob AP, Gurgel JL et al (2015) SLC46A3 is required to transport catabolites of noncleavable antibody maytansine conjugates from the lysosome to the cytoplasm. Cancer Res 75:5329–5340. https://doi.org/10.1158/0008-5472.CAN-15-1610

Article  CAS  PubMed  Google Scholar 

Tomabechi R, Kishimoto H, Sato T et al (2022) SLC46A3 is a lysosomal proton-coupled steroid conjugate and bile acid transporter involved in transport of active catabolites of T-DM1. PNAS Nexus 1:pgac063. https://doi.org/10.1093/pnasnexus/pgac063

Article  CAS  PubMed  PubMed Central  Google Scholar 

Min H-Y, Lee H-Y (2022) Molecular targeted therapy for anticancer treatment. Exp Mol Med 54:1670–1694. https://doi.org/10.1038/s12276-022-00864-3

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wolf G, Craigon C, Teoh ST et al (2025) The efflux pump ABCC1/MRP1 constitutively restricts PROTAC sensitivity in cancer cells. Cell Chem Biol 32:291-306.e6. https://doi.org/10.1016/j.chembiol.2024.11.009

Article  CAS  PubMed  Google Scholar 

Schumacher H, Smith RL, Williams RT (1965) The metabolism of thalidomide: the fate of thalidomide and some of its hydrolysis products in various species. Br J Pharmacol Chemother 25:338–351

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jarusiewicz JA, Yoshimura S, Mayasundari A et al (2023) Phenyl dihydrouracil: an alternative cereblon binder for PROTAC design. ACS Med Chem Lett 14:141–145. https://doi.org/10.1021/acsmedchemlett.2c00436

Article  CAS  PubMed  PubMed Central  Google Scholar