EP300 selective ProDeg

EP300 selective ProDeg is a heterobifunctional protein degrader (PROTAC) developed by Pfizer for the treatment of hematopoietic malignancies, such as multiple myeloma and non-Hodgkin lymphoma. It specifically targets EP300 (p300), a histone acetyltransferase that acts as a master regulator of transcription by modulating enhancer and promoter activity through histone acetylation (specifically H3K27 and H3K18). Unlike dual EP300/CREBBP inhibitors, which are often limited by dose-dependent thrombocytopenia, this selective degrader demonstrates greater than 100-fold selectivity for EP300 over its paralog CREBBP. This selectivity is intended to improve the therapeutic window and tolerability. In preclinical models, the compound induces rapid degradation of EP300, resulting in the downregulation of key oncogenic transcription networks, including MYC and IRF4, and significant tumor growth inhibition in xenograft models.

Other names

EP300 selective degraderEP-300 selective degraderEP 300 selective degraderEP300 selective PROTACEP-300 selective PROTACEP 300 selective PROTACEP300 selective heterobifunctional degraderEP-300 selective heterobifunctional degraderEP 300 selective heterobifunctional degrader