1. MAPK/ERK Pathway
  2. MEK
  3. GDC-0623

GDC-0623 (Synonyms: RG 7421; MEK inhibitor 1)

Cat. No.: HY-15610 Purity: 99.15%
Handling Instructions

GDC-0623 (RG 7421) is a potent, ATP-uncompetitive inhibitor of MEK1 (Ki=0.13 nM, +ATP), and displays 6-fold weaker potency against HCT116 (KRAS (G13D), EC50=42 nM) versus A375 (BRAFV600E, EC50=7 nM).

For research use only. We do not sell to patients.

GDC-0623 Chemical Structure

GDC-0623 Chemical Structure

CAS No. : 1168091-68-6

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 165 In-stock
Estimated Time of Arrival: December 31
5 mg USD 150 In-stock
Estimated Time of Arrival: December 31
10 mg USD 250 In-stock
Estimated Time of Arrival: December 31
50 mg USD 650 In-stock
Estimated Time of Arrival: December 31
100 mg USD 980 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

Based on 8 publication(s) in Google Scholar

Top Publications Citing Use of Products

    GDC-0623 purchased from MCE. Usage Cited in: Sci Signal. 2018 Oct 30;11(554). pii: eaar6795. 

    MEK1 mutants with in-frame deletions of the β3-αC loop exhibit differential resistance to MEK inhibitors (Trametinib, GDC0623, cobimetinib, AZD6244, and binimentinib).

    View All MEK Isoform Specific Products:

    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    GDC-0623 (RG 7421) is a potent, ATP-uncompetitive inhibitor of MEK1 (Ki=0.13 nM, +ATP), and displays 6-fold weaker potency against HCT116 (KRAS (G13D), EC50=42 nM) versus A375 (BRAFV600E, EC50=7 nM).

    IC50 & Target

    MEK1

    0.13 nM (Ki, +ATP)

    In Vitro

    GDC-0623 (RG 7421) and G-573 are able to prevent MEK phosphorylation by CRAF in vitro, and able to block MEK phosphorylation by BRAF(V600E)[1]. GDC-0623 (RG 7421) is potent, ATP-uncompetitive inhibitors of MEK1 but shows distinct shifts in cellular activity compared with the other two inhibitors, only 6-fold half-maximum effective concentration (EC50) decreases[2].

    In Vivo

    GDC-0623 (RG 7421) (40 mg/kg, p.o.) shows percent tumour growth inhibition (%TGI) in MiaPaCa-2 xenograft model. GDC-0623 (RG 7421) and G-573 show superior antitumour activity compared to GDC-0623 (RG 7421) in all three KRAS models[1].

    Clinical Trial
    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 30 mg/mL (65.76 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.1920 mL 10.9599 mL 21.9197 mL
    5 mM 0.4384 mL 2.1920 mL 4.3839 mL
    10 mM 0.2192 mL 1.0960 mL 2.1920 mL
    *Please refer to the solubility information to select the appropriate solvent.
    References
    Cell Assay
    [1]

    Flag-MEK1 mutants, S212P and S212A, are generated using the QuickChange site directed mutagenesis kit. Mammalian expression vectors for N-terminal Flag tagged MEK-1 are expressed in HCT116 cells. 1.8×106 HCT116 cells are plated in 10 cm plate and transfected on the following day with 17 μg of expression constructs using lipofectamine 2000. After 48 hours cells are treated with inhibitors for the indicated times, harvested and lysed in 100 μL cell extraction buffer. Cell lysates from each sample are analyzed by SDS-PAGE. Membranes are incubated with phospho-MEK S221, phospho-ERK1/2 and MEK1 primary antibodies and immunoreactive proteins are analyzed by SuperSignal West Pico Chemiluminescent Substrate.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Colo205 xenografts are established by inoculating 5×106 cells resuspended in Hank's Balanced Salt Solution (HBSS) subcutaneously (s.c.) in the rear right flank of 6-8 week old female nude (nu/nu) mice. NCI-H2122 xenografts are established by inoculating 1×107 cells resuspended in Hank's Balanced Salt Solution (HBSS) plus matrigel (growth factor reduced) s.c. in the rear right flank of 6-8 week old female nu/nu mice. Both A375 and MiaPaca-2 xenografts are initiated by transplanting 1 mm3 tumor fragments from their respective passaged tumors s.c. into the flank of athymic nu/nu mice. When tumors reached appr 200 mm3, mice are randomized and treated with daily (QD) oral gavage (PO) with either vehicle [methylcellulose 0.1% tween 80 0.1% (MCT)], GDC-0973 (at 10 mg/kg), GDC-0623 (RG 7421) (40 mg/kg), or G-573 (100 mg/kg). All doses of MEK inhibitors represented maximal tolerated doses (MTDs), resulting in no more than 15-20% body weight loss. Tumor volumes are determined using digital calipers using the formula (L×W×W)/2. Tumor growth inhibition (%TGI) iscalculated as the percentage of the area under the fitted curve (AUC) for the respective dose group per day in relation to the vehicle. Animal weights are recorded twice per week and mice are removed from study if body weights dropped ≥20%. Partial responses (PRs) are defined as any tumor demonstrating a ≥ 50% decrease in tumor volume, whereas complete responses (CRs) are defined as any tumor demonstrating 100% reduction in tumor volume at any point during the study.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    456.21

    Formula

    C₁₆H₁₄FIN₄O₃

    CAS No.

    1168091-68-6

    SMILES

    FC(C=C(I)C=C1)=C1NC2=C(C(NOCCO)=O)C=CC3=CN=CN23

    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.15%

    • Molarity Calculator

    • Dilution Calculator

    The molarity calculator equation

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass   Concentration   Volume   Molecular Weight *
    = × ×

    The dilution calculator equation

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
    × = ×
    C1   V1   C2   V2

    Inquiry Online

    Your information is safe with us. * Required Fields.

    Product name

     

    Salutation

    Applicant name *

     

    Email address *

    Phone number *

     

    Organization name *

    Country or Region *

     

    Requested quantity *

    Remarks

    Bulk Inquiry

    Inquiry Information

    Product Name:
    GDC-0623
    Cat. No.:
    HY-15610
    Quantity:

    GDC-0623

    Cat. No.: HY-15610