Curaxins are small molecules that simultaneously activate p53 and inhibit NF-κB without causing detectable genotoxicity. CBL0137 is a water soluble and metabolically stable curaxin that activates p53 with an EC50 value of 0.37 μM and inhibits NF-κB with an EC50 value of 0.47 μM. It functionally inactivates the facilitates chromatin transcription complex, driving the effects on p53 and NF-κB and promoting cancer cell death. CBL0137 has broad anticancer activity in mice when administered orally, eradicates drug-resistant cancer stem cells, and potentiates efficacy of gemcitabine in preclinical models of pancreatic cancer.
