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Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49
Graphical Abstract
Figure 1: Mechanism of a PROTAC-mediated targeted protein degradation. Created in BioRender. Wu, M. (2026) ht...
Figure 2: CDK4/6 PROTACs with alkyl or PEG chains as linkers.
Figure 3: CDK4/6 PROTACs with triazole-containing linkers.
Figure 4: Structures of AT-7519 (7) and FN-1501 (8), and CDK9 degrading PROTACs based on compound 8 with vari...
Figure 5: CDK9 PROTACs with alkane chain as linkers or triazole linkers.
Figure 6: Structures of HDAC6 inhibitors ACY1215 (17) and ACY-241 (18), as well as the structure of PROTACs 1...
Figure 7: C4-linked-series and C5-linked-series of HDAC6 PROTACs.
Figure 8: Structures of VHL-based degraders.
Figure 9: Structures of VHL-based and CRBN-based selective HDAC PROTACs.
Figure 10: Structures of the “amide series” and “phenyl series” PROTACs studied by Crews et al.
Figure 11: Structures of the “amide series” PROTACs.
Figure 12: Structures of the “phenyl series” PROTACs.
Figure 13: Structures of JQ1 (34) and MZ1 (35).
Figure 14: Structures of macro-PROTAC-1 and SHD913.
Figure 15: Commonly utilized thalidomide-derived CRBN ligands and possible linker attachment styles. A1, A2: p...
Figure 16: VHL ligands frequently used in PROTACs. Linker attachment options are represented with curly bonds ...
Figure 17: Varying the inhibitor warhead and the recruited E3 ligase permits targets to be accessed for degrad...
Figure 18: Structures of YX-2-233 (42) and YX-2-107 (43).
Figure 19: Structures of compounds 44 and 45.
Figure 20: Design of the SGK3 PROTACs.
Figure 21: CRBN, VHL, and IAP ligands used when designing HDAC-PROTACs.
Figure 22: CDK4/6-PROTACs with different E3 ligands targeting the same E3 ubiquitin ligase.
Figure 23: Structural basis for the selective degradation of CDK6 over CDK4 by PROTAC 2. (A) CDK4–molecule 2–C...
Figure 24: Regarding the PPI-driven selectivity mechanism of two PROTAC molecules, SJF-α and SJF-δ, for p38α a...
Figure 25: Co-crystal structure and ultra-high selectivity of the STAT6 PROTAC degrader AK-1690. (A) STAT6–AK-...