1. Protein Tyrosine Kinase/RTK
  2. c-Met/HGFR
    FLT3
    ROS
    Discoidin Domain Receptor
  3. Merestinib dihydrochloride

Merestinib dihydrochloride (Synonyms: LY2801653 dihydrochloride)

Cat. No.: HY-15514A Purity: 99.02%
Handling Instructions

Merestinib dihydrochloride (LY2801653 dihydrochloride) is a potent, orally bioavailable c-Met inhibitor (Ki=2 nM) with anti-tumor activities. Merestinib dihydrochloride also has potent activity against MST1R (IC50=11 nM), FLT3 (IC50=7 nM), AXL (IC50=2 nM), MERTK (IC50=10 nM), TEK (IC50=63 nM), ROS1, DDR1/2 (IC50=0.1/7 nM) and MKNK1/2 (IC50=7 nM).

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

Merestinib dihydrochloride Chemical Structure

Merestinib dihydrochloride Chemical Structure

CAS No. : 1206801-37-7

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 248 In-stock
Estimated Time of Arrival: December 31
5 mg USD 180 In-stock
Estimated Time of Arrival: December 31
10 mg USD 264 In-stock
Estimated Time of Arrival: December 31
50 mg USD 732 In-stock
Estimated Time of Arrival: December 31
100 mg USD 1080 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 5 publication(s) in Google Scholar

Other Forms of Merestinib dihydrochloride:

Top Publications Citing Use of Products

    Merestinib dihydrochloride purchased from MCE. Usage Cited in: Cancer Discov. 2016 Dec;6(12):1334-1341.

    The MET D1228V mutation renders all type I MET inhibitors ineffective, as evidence by the failure of Savolitinib, PF-02341066, and INC280 to inhibit MET phosphorylation. In contrast, type II MET inhibitors XL184, MGCD265, and Merestinib (LY2801653) are able to effectively suppress MET phosphorylation in the presence of the D1228V mutation.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Merestinib dihydrochloride (LY2801653 dihydrochloride) is a potent, orally bioavailable c-Met inhibitor (Ki=2 nM) with anti-tumor activities. Merestinib dihydrochloride also has potent activity against MST1R (IC50=11 nM), FLT3 (IC50=7 nM), AXL (IC50=2 nM), MERTK (IC50=10 nM), TEK (IC50=63 nM), ROS1, DDR1/2 (IC50=0.1/7 nM) and MKNK1/2 (IC50=7 nM)[1][2].

    IC50 & Target

    Ki: 2 nM (c-Met)[1]
    IC50: 11 nM (MST1R), 7 nM (FLT3), 2 nM (AXL), 10 nM (MERTK), 63 nM (TEK), 0.1/7 nM (DDR1/2), 7 nM (MKNK1/2)[1]

    In Vitro

    Merestinib (LY2801653) also inhibits MST1R (IC50=11 nM), AXL (IC50=2 nM), MERTK (IC50=10 nM), TYRO3 (IC50=28 nM), ROS1, PDGFRA (IC50=41 nM), FLT3 (IC50=7 nM), TEK (IC50=63 nM), DDR1/2 (IC50=0.1/7 nM) and MKNK1/2 (IC50=7 nM)[1].
    Merestinib demonstrates effects on MET pathway-dependent cell scattering and cell proliferation. The mean IC50 value (n=6 determinations) of Merestinib for inhibition of MET auto-phosphorylation in HGF-stimulated H460 cells is 35.2±6.9 nM and the IC50 for MET auto-phosphorylation in S114 cells is 59.2 nM. Transfection with the MET variants confers growth-factor independence and treatment with Merestinib inhibits growth of these MET variant clones with an IC50 ranging from 3-fold more potent (V1092I) to approximately 6-fold less potent (L1195V) compare with the growth inhibition of cells with the MET wild-type sequence[1].
    Merestinib (2, 5, and 10 μM) reduces the number of viable TFK-1 and SZ-1 cells in a dose and time dependent manner, and significant inhibits wound healing for TFK-1 and SZ-1 cell lines. Merestinib inhibits cell invasion in TFK-1 and SZ-1 cells in a concentration dependent manner[2].

    In Vivo

    Merestinib (LY2801653) demonstrates anti-tumor effects in MET amplified (MKN45), MET autocrine (U-87MG, and KP4) and MET over-expressed (H441) xenograft models; and in vivo vessel normalization effects. Merestinib (LY2801653) is a type-II ATP competitive, slow-off inhibitor of MET tyrosine kinase with a pharmacodynamic residence time (Koff) of 0.00132 min-1 and t1/2 of 525 min. Merestinib (LY2801653) treatment inhibits MET phosphorylation with a composite TED50 (50 % target inhibition dose) of 1.2 mg/kg and a composite TED90 (90 % target inhibition dose) of 7.4 mg/kg[1]. Merestinib (LY2801653) (20 mg/kg) reduces TFK-1 tumor growth significantly relative to vehicle control. Merestinib (LY2801653) inhibits the growth of intra- and extrahepatic CCC xenograft tumors[2].

    Clinical Trial
    Molecular Weight

    625.45

    Formula

    C₃₀H₂₄Cl₂F₂N₆O₃

    CAS No.

    1206801-37-7

    SMILES

    [H]Cl.[H]Cl.O=C(C1=CC=C(C)N(C2=CC=C(F)C=C2)C1=O)NC3=CC=C(OC4=CC5=C(N(C)N=C5)C=C4C6=CNN=C6)C(F)=C3

    Shipping

    Room temperature in continental US; may vary elsewhere.

    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 : ≥ 100 mg/mL (159.88 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.5988 mL 7.9942 mL 15.9885 mL
    5 mM 0.3198 mL 1.5988 mL 3.1977 mL
    10 mM 0.1599 mL 0.7994 mL 1.5988 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (4.00 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 2.5 mg/mL (4.00 mM); Clear solution

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (4.00 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Kinase Assay
    [1]

    The Ki value and mode of inhibition of LY2801653 for the MET kinase activity are determined using a radiometric filter-binding assay. Reactions are carried out in 96-well plates in Enzyme dilution buffer (EDB) compose of 50 mM Tris HCl pH 7.5, 2 mM DTT, 0.005% Triton X-100, 10 mM MgCl2, and 250 μM EDTA. Serially diluted LY2801653 (final concentration 250 to 0 nM) are followed by the addition of a series of 8 concentrations of 33P-γ-ATP (final concentration 400 to 10 μM ATP), and 5 nM enzyme (final concentration). After a 2-hour incubation, PolyGluTyr synthetic protein substrate (final 150 μg/mL) is added to initiate the 30-minute kinase reaction. Reactions are quenched with 10% H3PO4, transfer to a pre-wetted Multiscreen anionic phosphocellulose 96-well filter plate, and washed; radioactivity is measured with a scintillation counter. The experimental data are fit to a global mix model inhibition equation using GraphPad Prism softwar to generate an alpha value to determine the modality of inhibition and to calculate the Ki value for LY2801653[1].

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

    Cell Assay
    [1]

    H460 cells are cultured in RPMI media supplemented with 10% FBS and plated (prior to becoming 70% confluent) in 96-well plates at 20,000 cells/well and are incubated overnight at 37°C. The next day, the cells are incubated with RPMI-1640 in low serum (0.5% FBS) for 2 hours prior to treatment with Merestinib. Thirty minutes after the addition of Merestinib (LY2801653), HGF at a final concentration of 100ng/mL is added. After a 10-minute incubation, cell lysates are prepared and pMET is quantified. Relative IC50 values are determined using MSD activity units by calculating the percentage of inhibition with respect to on-plate MIN (unstimulated) and MAX controls and then fitting the percentage-of-inhibition values and 10-point dose response data to a 4-parameter logistic equation using ActivityBase[1].

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

    Animal Administration
    [1]

    S114 cells are implanted subcutaneously onto female athymic nude mice. For dose response evaluation, on day 8 after the implantation, Merestinib (LY2801653) is given at a range of 0.75 mg/kg to 100 mg/kg (n=8 per dose group). At 2 hours after dose, blood samples and tumors are collected and flash frozen. For time course study, Merestinib (LY2801653) is given at 12 mg/kg (n=10 per time point). Animals are sacrificed at 2, 8, 16, and 24 hours after dose, and blood samples and tumors are collected. pMET is measured in the S114 tumor lysates using the MSD ELISA assay. Lysates are prepared from pulverized frozen tumor tissue, and homogenized with Lysing Matrix D beads, with addition of RIPA lysis buffer containing phosphatase and protease inhibitors. Protein concentration is determined using the DC protein assay kit. The pMET MSD ELISA assay is performed.

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

    References

    Purity: 99.02%

    • No file chosen (Maximum size is: 1024 Kb)
    • If you have published this work, please enter the PubMed ID.
    • Your name will appear on the site.
    • 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

    Keywords:

    MerestinibLY2801653LY 2801653LY-2801653c-Met/HGFRFLT3ROSDiscoidin Domain ReceptorCluster of differentiation antigen 135CD135Fms like tyrosine kinase 3Inhibitorinhibitorinhibit

    Your Recently Viewed Products:

    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:
    Merestinib dihydrochloride
    Cat. No.:
    HY-15514A
    Quantity:
    MCE Japan Authorized Agent: