GDC-0994 is an orally available small molecule inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2), highly selective for ERK1 and ERK2, with biochemical potency of 1.1 nM and 0.3 nM, respectively. Daily, oral dosing of GDC-0994 results in significant single-agent activity in multiple in vivo cancer models, including KRAS-mutant and BRAF-mutant human xenograft tumors in mice. PD biomarker inhibition of phospho-p90RSK in these tumors correlates with potency in vitro and in vivo. In contrast to other published ERK inhibitors, GDC-0994 neither increases nor decreases phospho-ERK, suggesting that different ERK inhibitors have alternative mechanisms of action with respect to feedback signaling. Furthermore, we demonstrate a novel approach for targeting the oncogenic signaling through the RAS pathway by combining ERK and MEK inhibitors.

KEYWORDS: GDC-0994 | Supplier | ERK1/2 inhibitor | Ravoxertinib | RG7842 | GDC0994 | GDC 0994 | RG 7842 | RG-7842 | CT-G0994 | CAS [1453848-26-4] | MAPK | ERK | Inhibitor | Enzymes