2. Protein Tyrosine Kinase/RTK Autophagy Apoptosis
  3. c-Met/HGFR Autophagy Apoptosis
  4. PHA-665752

PHA-665752 is a selective, ATP-competitive, and active-site inhibitor of the catalytic activity of c-Met kinase (Ki=4 nM; IC50=9 nM). PHA-665752 exhibits >50-fold selectivity for c-Met compared with a panel of diverse tyrosine and serine-threonine kinases. PHA-665752 induces apoptosis and cell cycle arrest, and exhibits cytoreductive antitumor activity.

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

PHA-665752 Chemical Structure

PHA-665752 Chemical Structure

CAS No. : 477575-56-7

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 106 In-stock
Solution
10 mM * 1 mL in DMSO USD 106 In-stock
Solid
1 mg USD 30 In-stock
5 mg USD 75 In-stock
10 mg USD 115 In-stock
25 mg USD 230 In-stock
50 mg USD 365 In-stock
100 mg USD 590 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

Based on 14 publication(s) in Google Scholar

Other Forms of PHA-665752:

PHA-665752 Related Antibodies

Top Publications Citing Use of Products

    PHA-665752 purchased from MedChemExpress. Usage Cited in: Am J Transl Res. 2023 Feb 28;15(2):896-913.

    PHA-665752 significantly decreases the migration rate at 24 h and 48 h in Huh-7R cells.

    PHA-665752 purchased from MedChemExpress. Usage Cited in: Respir Res. 2020 Aug 14;21(1):215.  [Abstract]

    Immunoblotting reveals that c-Met in the plasma membrane is phosphorylated in response to the binding of HGF, and this c-Met phosphorylation is abolished by PHA-665752 in the LPS-transfected endothelial cells.

    PHA-665752 purchased from MedChemExpress. Usage Cited in: Oncotarget. 2017 Jun 13;8(24):38717-38730.  [Abstract]

    KU812/IR cells are exposed to the indicated concentrations of Imatinib or PHA665752. After incubation for 48 h, the cytoplasmic fractions are extracted and then subjected to SDS-PAGE/immunoblotting with anti-phospho-MET, anti-phospho-ABL1, anti-phospho-ERK1/2, anti-phospho-AKT, anti-phospho-JNK, anti-MET, anti-ABL1, anti-ERK1/2, anti-AKT, and anti-JNK antibodies. Anti-β-ACTIN antibody is used as internal standards.

    • Biological Activity

    • Purity & Documentation

    • References

    • Customer Review

    Description

    PHA-665752 is a selective, ATP-competitive, and active-site inhibitor of the catalytic activity of c-Met kinase (Ki=4 nM; IC50=9 nM). PHA-665752 exhibits >50-fold selectivity for c-Met compared with a panel of diverse tyrosine and serine-threonine kinases. PHA-665752 induces apoptosis and cell cycle arrest, and exhibits cytoreductive antitumor activity[1][2].

    IC50 & Target

    Ki: 4 nM[1]
    IC50: 9 nM (c-Met)[1]
    In Vitro

    PHA-665752 is a potent and ATP-competitive inhibitor of c-Met kinase activity with a Ki of 4 nM and an IC50 of 9 nM[1].
    PHA-665752 exhibits >50-fold selectivity for c-Met enzyme compared with the majority of kinases evaluated[1].
    PHA-665752 shows potent inhibition of c-Met RTK autophosphorylation in NIH3T3 cells engineered to express high levels of c-Met and hepatocyte growth factor (HGF)[1].
    PHA-665752 inhibits HGF-stimulated or constitutive phosphorylation of mediators of downstream of c-Met such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK in multiple tumor cell lines[1].
    PHA-665752 (0-1.25 μM; 18 hours) potently inhibits HGF and c-Met-driven phenotypes such as cell growth (proliferation and survival), cell motility, invasion, and/or morphology of a variety of tumor cells[1].
    PHA-665752 (0-1.25 μM; 72 hours) induces apoptosis in both the presence and absence of HGF at concentrations that inhibited tyrosine phosphorylation of c-Met in GTL-16 cells[1].
    PHA-665752 (0.0125-0.2 μM; 4 hours) potent inhibits HGF-induced c-Met phosphorylation in A549 cells[1].

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

    PHA-665752 Related Antibodies

    Cell Proliferation Assay[1]

    Cell Line: S114 cells, GTL-16 cells, NCI-H441 cells, or BxPC-3 cells
    Concentration: 0 μM, 0.002 μM, 0.01 μM, 0.05 μM, 0.25 μM, 1.25 μM
    Incubation Time: 18 hours
    Result: Potently inhibited HGF and c-Met-driven cell growth.

    Apoptosis Analysis[1]

    Cell Line: GTL-16 cells
    Concentration: 0 μM, 0.002 μM, 0.01 μM, 0.05 μM, 0.25 μM, 1.25 μM
    Incubation Time: 72 hours
    Result: Induced apoptosis in both the presence and absence of HGF at concentrations that inhibited tyrosine phosphorylation of c-Met in GTL-16 cells. Immunoblot Analysis.

    Western Blot Analysis[1]

    Cell Line: A549 cells
    Concentration: 0.0125 μM, 0.025 μM,0.05 μM,0.1 μM,0.2 μM
    Incubation Time: 4 hours
    Result: Potent inhibited HGF-induced c-Met phosphorylation in A549 cells.
    In Vivo

    PHA-665752 (7.5-30 mg/kg/day; i.v. ; for 9 days) exhibits statistically significant dose-dependent tumor growth inhibition of 68%, 39%, and 20% of vehicle control at the 30 mg/kg/day, 15 mg/kg/day, and 7.5 mg/kg/day doses, respectively[1].
    PHA-665752 shows a potent cytoreductive activity in a gastric carcinoma xenograft model[1].

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

    Animal Model: Female athymic mice (nu/nu, 8–12 weeks) bearing S114 or GTL-16 tumor xenografts[1]
    Dosage: 7.5 mg/kg/day, 15 mg/kg/day, 30 mg/kg/day
    Administration: Intravenous injection; for 9 days
    Result: Demonstrated statistically significant dose-dependent tumor growth inhibition.
    Molecular Weight

    641.61

    Formula

    C32H34Cl2N4O4S
    CAS No.
    Appearance

    Solid

    Color

    Yellow to orange

    SMILES

    O=C(C1=C(NC(/C=C2C(NC3=C\2C=C(C=C3)S(=O)(CC4=C(C=CC=C4Cl)Cl)=O)=O)=C1C)C)N5[C@H](CCC5)CN6CCCC6
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMSO : 25 mg/mL (38.96 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.5586 mL 7.7929 mL 15.5858 mL
    5 mM 0.3117 mL 1.5586 mL 3.1172 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

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    • 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

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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 (3.90 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 (3.90 mM); Suspended solution; Need ultrasonic

      This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

      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
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    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).
    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: 99.86%

    COA (252 KB) LCMS (92 KB)

    Handling Instructions (2659 KB)
    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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.5586 mL 7.7929 mL 15.5858 mL 38.9645 mL
    5 mM 0.3117 mL 1.5586 mL 3.1172 mL 7.7929 mL
    10 mM 0.1559 mL 0.7793 mL 1.5586 mL 3.8964 mL
    15 mM 0.1039 mL 0.5195 mL 1.0391 mL 2.5976 mL
    20 mM 0.0779 mL 0.3896 mL 0.7793 mL 1.9482 mL
    25 mM 0.0623 mL 0.3117 mL 0.6234 mL 1.5586 mL
    30 mM 0.0520 mL 0.2598 mL 0.5195 mL 1.2988 mL
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    PHA-665752 Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      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.

    Keywords:

    PHA-665752477575-56-7PHA665752PHA 665752c-Met/HGFRAutophagyApoptosisInhibitorinhibitorinhibit

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