Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• other non-enzymatic proteins [7] are essentially undruggable using conventional inhibitor-based approaches [4][8]. Consequently, protein–protein interaction (PPI)-based targeted protein degradation (TPD) strategies have attracted increasing attention over the past two decades [9][10]. Among them

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• binding affinity comparable to CAM4066, confirming that linker installation is tolerated and preserves key interactions in the αD and ATP sites. Keywords: CAM4066; casein kinase 2 (CK2); PROTACs; targeted protein degradation; Introduction Protein kinases form a large family of more than 500 enzymes that

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• -selective degrader, and for the first time confirmed its ability to degrade the membrane-bound form of FGFR2. This work provides an innovative targeted protein degradation strategy for the treatment of FGFR2-driven tumors and holds significant potential for clinical application. Keywords: CRBN; erdafitinib

• condensed with the reported compound 6 [31] under EDCI to afford the final novel FGFR2 degrader. Screening and identification of LC-JD-6 as a potent FGFR2 degrader Targeted protein degradation molecules in degrading FGFR2 were tested in KATO III cells (high basal FGFR2), identifying LC-JD-6 as the optimal

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• drug”) class of PROTAC molecules with a PEG linker is frequently used to promote targeted protein degradation. The standard protocol for their synthesis involves nucleophilic aromatic substitution of 4-fluorothalidomide with a PEG-amine. We report herein the identification of a commonly ignored

• contamination. Keywords: glutarimide; IMiD; impurity; nucleophilic acyl substitution; PROTAC; Introduction Targeted protein degradation capitalizing on the concept of chemically induced dimerization has emerged as a new therapeutic approach recently [1]. In particular, the modularity of proteolysis targeting

• chimera (PROTAC) has made it a popular starting point to develop selective small-molecule degraders [2]. Currently, leveraging ubiquitination by the von Hippel–Lindau (VHL) protein or cereblon (CRBN) is the most successful method to achieve targeted protein degradation [3][4]. For initial studies, a short

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• ; Introduction Targeted protein degradation (TPD) has transformed the field of drug discovery [1][2]. Utilizing proximity-induced pharmacological strategies [3], this method has fostered the creation of numerous molecular glues and proteolysis-targeting chimeras (PROTACs). By manipulation of the internal