Extracellular signal-regulated kinases (Erks) act in the Ras-Raf-Mek-Erk signaling cascade and regulate various cellular processes such as cell growth, proliferation and survival in response to a variety of extracellular or intrinsically mutated upstream signals.
The study was intended to test AEZS-131 for selectivity, inhibition of Rsk-phosphorylation (cellular substrate of Erk), mode of action and cleavage of PARP.
The data demonstrated that AEZS 131 selectively inhibits Erk at low nanomolar (nM) concentrations and induces G1 arrest.
The cytotoxic effect of AEZS-131 was most pronounced in TNBC cell lines with mutations in the MAPK pathway.