Cobimetinib hemifumarate is a novel selective MEK1 inhibitor, and the IC50 value against MEK1 is 4.2 nM.
体外研究
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). Mitochondrial OXPHOS limits cell death induced by cobimetinib (100 nM) in melanoma with constitutive MAPK activation in A375 cells.
体内研究
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. 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 h, respectively. 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).
分子式
C46H46F6I2N6O8
分子量
589.25
CAS号
1369665-02-0
中文名称
考比替尼半富马酸盐
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 50 mg/mL (84.85 mM; Need ultrasonic)
H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)