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OTAVAchemicals Targeted CELMoDs Collection (1256 compounds in total) represents an innovative approach to targeted protein degradation, leveraging advanced molecular glue technologies. By stabilizing cereblon (CRBN) in its closed conformation, our compounds enhance CRBN’s ability to mediate the proteasomal degradation of target proteins. This mechanism involves the precise interaction of the thalidomide binding domain (TBD) and Lon protease-like domain (Lon), as demonstrated by reference compounds like CC-92480 (mezigdomide) and CC-220 (Iberdomide), which engage with the sensor loop of CRBN to promote target protein degradation.
Our CELMoDs Collection was developed by integrating key principles of structural biology and cheminformatics:
1. Reference Compound Selection: Known CELMoD structures were analyzed, focusing on their ability to stabilize CRBN’s closed conformation.
2. Molecular Docking and Screening: Using the structure of CRBN in its closed state (PDB: 8D7Z), molecular docking identified compounds with high binding potential to the TBD and Lon domains.
3. Cheminformatics Filters: MedChem properties and PAINS filters ensured the selection of drug-like and chemically viable compounds.
4. Diversity Clustering: Compounds were grouped into clusters, and diverse representatives were selected from each group.
5. Validation: Final compounds were assessed for their predicted ligand efficiency (LE) and ability to act as thalidomide warhead competitors.
The resulting library offers a curated collection of 1,256 compounds designed to expand the potential of CRBN-mediated degradation and drive the discovery of next-generation therapeutics.
CELMoDs library Divided into 4 Types:
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Long Core:
Compounds closely related to optimal docking modes, forming interactions with both TBD and Lon domains
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Long Diversity:
More diverse compounds loosely related to the best docking modes, forming interactions with both TBD and Lon domains
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High LE Core:
Compounds closely related to high ligand efficiency (LE) docking modes, mostly occupying the thalidomide's site in TBD
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High LE Diversity:
More diverse compounds loosely related to high ligand efficiency (LE) docking modes, mostly occupying the thalidomide's site in TBD
"Long" targeting both sites: "High LE" targeting thalidomide site:
All the compounds are in stock, cherry-picking is available.
The libraries (DB, SD, XLS, PDF format) as well as the price-list are available on request. Feel free to contact us or use on-line form below to send an inquiry if you are interested to obtain this library or if you need more information.
Request Your Library Today! Fill out the form:
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