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

Merestinib dihydrochloride  (Synonyms: LY2801653 dihydrochloride)

Cat. No.: HY-15514A Purity: 99.36%
COA 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
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 182 In-stock
Solution
10 mM * 1 mL in DMSO USD 182 In-stock
Solid
5 mg USD 132 In-stock
10 mg USD 180 In-stock
50 mg USD 540 In-stock
100 mg USD 768 In-stock
200 mg   Get quote  
500 mg   Get quote  

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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 MedChemExpress. Usage Cited in: Cancer Discov. 2016 Dec;6(12):1334-1341.  [Abstract]

    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.

    View All Discoidin Domain Receptor Isoform Specific Products:

    • 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].

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

    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].

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

    Clinical Trial
    Molecular Weight

    625.45

    Formula

    C30H24Cl2F2N6O3

    CAS No.
    Appearance

    Solid

    Color

    White to light yellow

    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

    4°C, sealed storage, away from moisture

    *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 100 mg/mL (159.88 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    *"≥" 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
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    • Molarity Calculator

    • Dilution Calculator

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

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 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

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 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

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

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    Dosing volume
    (per animal)

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    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
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    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

    *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.36%

    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

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.5988 mL 7.9942 mL 15.9885 mL 39.9712 mL
    5 mM 0.3198 mL 1.5988 mL 3.1977 mL 7.9942 mL
    10 mM 0.1599 mL 0.7994 mL 1.5988 mL 3.9971 mL
    15 mM 0.1066 mL 0.5329 mL 1.0659 mL 2.6647 mL
    20 mM 0.0799 mL 0.3997 mL 0.7994 mL 1.9986 mL
    25 mM 0.0640 mL 0.3198 mL 0.6395 mL 1.5988 mL
    30 mM 0.0533 mL 0.2665 mL 0.5329 mL 1.3324 mL
    40 mM 0.0400 mL 0.1999 mL 0.3997 mL 0.9993 mL
    50 mM 0.0320 mL 0.1599 mL 0.3198 mL 0.7994 mL
    60 mM 0.0266 mL 0.1332 mL 0.2665 mL 0.6662 mL
    80 mM 0.0200 mL 0.0999 mL 0.1999 mL 0.4996 mL
    100 mM 0.0160 mL 0.0799 mL 0.1599 mL 0.3997 mL
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      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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