1. MAPK/ERK Pathway
  2. MEK

Cobimetinib (Synonyms: GDC-0973; XL518)

Cat. No.: HY-13064 Purity: 99.38%
Handling Instructions

Cobimetinib is a novel selective MEK inhibitor, and the IC50 value against MEK1 is 4.2 nM.

For research use only. We do not sell to patients.
Cobimetinib Chemical Structure

Cobimetinib Chemical Structure

CAS No. : 934660-93-2

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 112 In-stock
5 mg USD 96 In-stock
10 mg USD 120 In-stock
50 mg USD 396 In-stock
100 mg USD 576 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Other Forms of Cobimetinib:

    Cobimetinib purchased from MCE. Usage Cited in: J Control Release. 2015 Oct 21;220(Pt A):160-168.

    In vitro cytotoxicity analysis on HCT 116 cells showing enhanced cancer cell cytotoxicity of NCL and Cobimetinib combinations
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Cobimetinib is a novel selective MEK inhibitor, and the IC50 value against MEK1 is 4.2 nM.

    IC50 & Target

    IC50: 4.2 nM (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].

    Clinical Trial
    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 1.8821 mL 9.4107 mL 18.8214 mL
    5 mM 0.3764 mL 1.8821 mL 3.7643 mL
    10 mM 0.1882 mL 0.9411 mL 1.8821 mL
    Please refer to the solubility information to select the appropriate solvent.
    Animal Administration
    [3]

    GDC-0973 is formulated in water.

    5 million WM-266-4 melanoma cells are 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 120 mm3 are 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 are given a single oral dose of vehicle (water for injection USP), 1, 3, or 10 mg/kg of Cobimetinib (GDC-0973, expressed as free base equivalents). Mice in the multiple dose groups are 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) are 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 are stored at −80°C until analysis. GDC-0973 concentrations in plasma and tumor lysates are determined using liquid chromatography/tandem mass spectrometry (LC/MS-MS). The dynamic range of the assay is 0.004 to 35 μM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    531.31

    Formula

    C₂₁H₂₁F₃IN₃O₂

    CAS No.

    934660-93-2

    SMILES

    OC1([[email protected]]2NCCCC2)CN(C1)C(C3=C(C(F)=C(C=C3)F)NC4=C(C=C(C=C4)I)F)=O

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    10 mM in DMSO

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Purity: 99.38%

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    Inquiry Information

    Product Name:
    Cobimetinib
    Cat. No.:
    HY-13064
    Quantity: