Cobimetinib_racemate_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Libraries
Data Sheet
BIOLOGICAL ACTIVITY:
Cobimetinib(GDC–0973; XL518) is a potent, highly selective inhibitor of MEK1/2.
IC50 value:
Target: 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].
PROTOCOL (Extracted from published papers and Only for reference)
Animal administration [3]
5 million WM–266–4 melanoma cells were resuspended in Hank balanced salt solution and implanted intradermally into the hind flank of female NCR nude mice On days 11 or 13 after the implantation, xenograft mice with tumor volumes of approximately 100 to 120mm3 were randomly assigned to 8 groups (n = 27 per group), 4 single dose groups and 4 multiple dose groups. One day after randomization and group assignment, mice in the single dose groups were given a single oral dose of vehicle (water for injection USP), 1, 3, or 10 mg/kg of GDC–0973 (expressed as free base equivalents). Mice in the multiple dose groups were given daily oral doses of vehicle (water for injection USP), 1, 3, or 10 mg/kg of GDC–0973 for 14 days. Plasma and tumor samples (n = 3 per time point) were collected from euthanized mice predose and at 2, 4, 8, 16, 24, 72, 120, and 168 hours postdose on day 1 (single dose
groups) or day 14 (multiple dose groups). Samples were stored at –80°C until analysis. GDC–0973 concentrations in plasma and tumor lysates were determined using liquid chromatography/tandem mass spectrometry (LC/MS–MS). The dynamic range of the assay was 0.004 to 35 μM. ERK1/2 phosphorylation was determined by Western blot analysis.
References:
[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
Product Name:
Cobimetinib (racemate)Cat. No.:
HY-13078CAS No.:
934662-91-6Molecular Formula:
C 21H 21F 3IN 3O 2Molecular Weight:
531.31Target:
MEK Pathway:
MAPK/ERK Pathway Solubility:
DMSO: ≥ 40 mg/mL
MEK inhibitor. Clin Cancer Res. 2012 Jun 1;18(11):3090–9.
Caution: Product has not been fully validated for medical applications. For research use only.
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