PBS-1086 is a novel dual inhibitor of the canonical and noncanonical NF-κB pathways, increasing the magnitude and duration of initial EGFR inhibitor response in multiple NSCLC models, decreasing PDHK1 expression, and suppressing phosphorylation of the PDHK1 protein substrate PDHA1 in a panel of PTEN-deficient cell lines.
Metformin embonate is an AMP-activated protein kinase (AMPK) activator that improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose.
PLX7683 is a paradox breaker. Paradox breakers overcame several known mechanisms of resistance to first-generation RAF inhibitors. Dissociating MAPK pathway inhibition from paradoxical activation might yield both improved safety and more durable efficacy than first-generation RAF inhibitors