Protein Degraders

  Rationally designed heterobifunctional molecules (PROTACs) consisting of two small-molecule binders connected by an elongated linker can induce favorable proximity between a target protein and an E3 ubiquitin ligase which promotes polyubiquitination and degradation by the 26S proteasome. Asinex has created a tool box of useful PROTAC design components: E3 ligase ligands, bifunctional linkers, and their derivatives. These PROTAC components facilitate the creation of novel, cell permeable heterobifunctional protein degraders.

Please visit our e-Shop for available compounds used to design novel PROTACs.

  In addition to PROTACs, there are several other types of bifunctional compounds that promote the interaction of two (or more) proteins known as “molecular glues.” Molecular glue compounds are structurally distinct from PROTACs but they can also promote the formation of a multimeric complex with more than one target protein while inducing a favorable orientation and intramolecular interaction between binding partners. The scope of potential biological functions regulated by this phenomenon is extensive: signaling activation; apoptosis induction; protease assembly, transcriptional activation, transcription elongation, gene silencing, protein degradation, immune system direction, protein destabilization, transporter inhibition, PPI disruption and inhibition [1]. The rational design of small molecule molecular glues remains challenging although several chemotypes have been discovered through screening efforts including natural product-derived macrocycles (e.g. rapamycin-inspired), phthalimide-based derivatives (e.g. lenalidomide); and aryl sulfonamides (e.g. indisulam) and some others [2]. In order to facilitate the identification and development of new molecular glue compounds we have assembled a library of analogs of literature-reported molecular glue degraders: Thalidomide, Lenalidomide, Pomalidomide, Avadomide, 5-hydroxythalidomide, FPFT-2216, Iberdomide, CC-647, CC-3060, CC-92480, CC-885, CC-90009, ZXH-1-161, Indisulam, E7820, Tasisulam, chloroquinoxaline sulfonamide, dCeMM1, CR8, dCeMM2, dCeMM3, dCeMM4, HQ461.

1. Gerry, C.J., Schreiber, S.L. Unifying principles of bifunctional, proximity-inducing small molecules. Nat Chem Biol 16, 369–378 (2020). https://doi.org/10.1038/s41589-020-0469-1

2. Kozicka and Thoma, Haven’t got a glue: Protein surface variation for the design of molecular glue degraders, Cell Chemical Biology (2021), https://doi.org/10.1016/j.chembiol.2021.04.009

Product Name: Format/Size Descriptions Download
Protein Degraders
72 compounds
For cherry-picking
Update: 2022-04
Cereblon (CRBN)-binding building blocks that are commonly used in the design of protein degradation bifunctional molecules. We favored molecules that are underrepresented among other publicly available screening collections while maintaining a balance of structural diversity and complexity.
Molecular Glues 1257 compounds
For cherry-picking
Update: 2022-04
A library of analogs of literature-reported molecular glues including phthalimide-based derivatives (e.g. lenalidomide); aryl sulfonamides (e.g. indisulam) and some others.

Ludmila Sadovenko

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