Raw data related to Locking CBL TKBD in its native conformation presents a novel therapeutic opportunity in mutant CBL-dependent leukemia

Casitas B-lineage lymphoma (CBL) negatively regulates receptor protein tyrosine kinases (RTKs). Deleterious CBL mutants lose their E3 ubiquitin ligase activity and gain function as adaptors to cause myeloproliferative diseases. Currently, no targeted treatment is available for patients with CBL mutant-dependent diseases. We discovered a nanomolar-affinity peptide inhibitor, CBLock, by using a combination of phage-display technology and structure-based optimization. CBLock binds the substrate-binding pocket in CBL’s N-terminal tyrosine kinase binding domain (TKBD). The interaction between CBL mutants and RTKs could be disrupted by CBLock, thereby impairing the adaptor function of CBL mutants and downstream RTK signaling pathways. Therefore, inhibiting CBL TKBD in its native state presents a promising therapeutic opportunity in targeting mutant CBL-dependent blood cancers. Here, we present the western blot and SDS-PAGE raw data related to this work.