Biological Activity
Cobimetinib (GDC-0973, RG7420) is a potent, selective and oral MEK inhibitor with an IC50 of 4.2 nM for MEK1.
In Vitro
The EC50 values of Cobimetinib (GDC-0973) for 888MEL and A2058 cells are 0.2 μM, 10 μM, respectivelly. Melanoma cells are treated with EC50 concentration of MEK and PI3K inhibitors for 24 hours (888MEL: 0.05 μM GDC-0973, 2.5 μM GDC-0941; A2058: 2.5 μM GDC-0973, 2.5 μM GDC-0941)[1]. Mitochondrial OXPHOS limits cell death induced by cobimetinib (100 nM) in melanoma with constitutive MAPK activation in A375 cells[4].
In Vivo
In the NCI-H2122 KRASG12C mutant non-small cell lung carcinoma (NSCLC) xenograft model, treatment with up to 5 mg/kg Cobimetinib (GDC-0973) lead to moderate TGI and at 10 mg/kg approaches tumor stasis[1]. GDC-0973 and GDC-0941 are administered to A2058 tumor-bearing mice daily (QD) or every third day (Q3D) either as single agents or in combination. The population rate constants associated with tumor growth inhibition for GDC-0973 and GDC-0941 are 0.00102 and 0000651 μM-1 h-1, respectively[2]. Following single doses of GDC-0973 (1, 3, or 10 mg/kg, p.o.) estimated in vivo IC50 values of %pERK decrease based on tumor concentrations in xenograft mice are 0.78 (WM-266-4) and 0.52 μM (A375)[3].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.