Targeting WDR5 WBM Pocket. The interaction between WDR5 WBM pocket (highlighted by orange color in Figure ) and MYC is involved in MYC's association with chromatin and required for its oncogenic function in cancers . Disrupting the WDR5-MYC interaction might be a promising approach for targeting MYC through WDR5, as a few WBM pocket binders have been identified and published by the Fesik lab and us . How MYC peptide and these known small molecules bind to WBM pocket is presented by the zoom-in diagram in the right panel of Figure . These small molecules or their corresponding original hits were acquired through wet lab experimental activities such as fragment-based screening or high throughput biochemical screening. Taken together, the biological significance of targeting this WBM pocket in MYC or WDR5 related diseases, the knowledge of existing screening results and the feasibility of using the validated binders as the benchmark really makes it a good case study to validate the Pocket Crafter workflow that we elucidated in Figure . Diverse Scaffold Generation through Pocket Crafter. In order to explore the chemical space beyond the existing chemical matters for the WDR5 WBM pocket, we employed the Pocket Crafter workflow (depicted in Figure ). This innovative methodology allows for the generation of molecular entities tailored to complement the unique 3D topology of specific protein pockets. To achieve this, we utilized 3D generative chemistry model with the known tertiary structure of WDR5 (PDB: 8F1G) , and successfully generated an expansive library consisting of 543,491 distinct and valid structures, thereby significantly expanding the diversity of chemical entities available for investigation in this context.