Cobimetinib racemate

• CAT Number: I005552
• CAS Number: 934662-91-6
• Molecular Formula: C21H21F3IN3O2
• Molecular Weight: 531.31
• Purity: ≥95%
• Target: MEK1/2
• Solubility: DMSO: ≥ 40 mg/mL
• Storage: Store at -20°C

Cobimetinib(GDC-0973; XL518) is a potent, highly selective inhibitor of MEK1/2.


in vitro: The combination of GDC-0973 with the PI3K inhibitor GDC-0941 resulted in combination efficacy in vitro and in vivo via induction of biomarkers associated with apoptosis, including Bcl-2 family proapoptotic regulators [1].


in vivo: The population rate constants associated with tumor growth inhibition for GDC-0973 and GDC-0941 were 0.00102 and 0000651 μM(-1) h(-1), respectively. Using the model based on single-agent and QD combination efficacy data, simulations adequately described the tumor growth from the Q3D combination regimen [2]. Following single doses of GDC-0973, estimated in vivo IC(50) values of %pERK decrease based on tumor concentrations in xenograft mice were 0.78 (WM-266-4) and 0.52 μmol/L (A375) [3].

Reference

[1]. Hoeflich KP, et al. Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition. Cancer Res. 2012 Jan 1;72(1):210-9. 


[2]. Choo EF, et al. PK-PD modeling of combination efficacy effect from administration of the MEK inhibitor GDC-0973 and PI3K inhibitor GDC-0941 in A2058 xenografts. Cancer Chemother Pharmacol. 2013 Jan;71(1):133-43.


[3]. Wong H, et al. Bridging the gap between preclinical and clinical studies using pharmacokinetic-pharmacodynamic modeling: an analysis of GDC-0973, a MEK inhibitor. Clin Cancer Res. 2012 Jun 1;18(11):3090-9.