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. 2022 Aug 1;10:934337. doi: 10.3389/fchem.2022.934337

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Copyright © 2022 Qin, Dai and Wang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Factors influence the selectivity of degraders. (A) PROTAC with different linker attachment point to the VHL ligand selectively degrade p38α and p38β. (B) Structure of IRAK/Ikaros/Aiolos multi-targets degrader I-208 and WDR5/Ikaros/Aiolos multi-targets degrader MS40. (C) Bcl-2/Bcl-xL dual degradation by 753bR achieved with different linker attachment points to warhead; and crystal structure of Navitoclax with BCL-2 (Souers et al., 2013) with four pockets indicated with an arrow. The crystal structure was processed with PyMOL. (D) Trivalent PROTAC with multi-protein or multi-domain binding warheads. MZ1 with a preference for BRD4 degradation, SIM1 with a preference for BRD2 degradation.