The first-in-class BMI-1 modulators PTC-028 and PTC596 display potent activity in pre-clinical models of multiple myeloma

Abstract

Future progress in the treatment of multiple myeloma (MM) requires both the characterization of key drivers of the disease and novel, innovative approaches to tackle these vulnerabilities. Initially linked to the pathogenesis of MM more than a decade ago, with close associations to high-risk genes such as MYC and FOXM1, the polycomb group protein BMI-1 is a prominent example of oncogenic factors without a suitable clinical grade inhibitor. Here, we analyzed the pre-clinical activity of the first in class BMI-1 modulators PTC-028 and PTC596 using a comprehensive set of in vitro and in vivo models.