SCH772984

SCH772984 is a highly selective and ATP-competitive ERK inhibitor, with IC₅₀s of 4 and 1 nM for ERK1 and ERK2, respectively. SCH772984 has antitumor activity in MAPK inhibitor-na?ve and MAPK inhibitor-resistant cells containing BRAF or RAS mutations^[1]. IC50 & Target: IC50: 4/1 nM (ERK1/2)^[1] In Vitro: SCH772984 (300 nM; 24-48hours) results in a G1 arrest in SCH772984-sensitive melanoma cells^[1].
SCH772984 (3-300 nM; 24 hours) inhibits ERK and RSK phosphorylation^[1].
SCH772984 shows EC₅₀ values less than 500 nM in approximately 88% and 49% of BRAF-mutant (n=25) or RAS-mutant (n=35) tumor lines, respectively^[1]. In Vivo: SCH772984 (12.5-50 mg/kg; i.p.; twice daily for 14 days) leads to 98% tumor regression^[1].
Dose-dependent antitumor activity is also observed in the KRAS-mutant pancreatic MiaPaCa model, with 36% regression at 50 mg/kg twice daily. Importantly, tumor regression is accompanied by robust inhibition of ERK phosphorylation in tumor tissue. SCH772984 is well tolerated on this schedule as measured by morbidity, lethality, or body weight loss^[1].