1. Protein Tyrosine Kinase/RTK Metabolic Enzyme/Protease
  2. SHP2 Phosphatase
  3. SHP099

SHP099 est un inhibiteur puissant de SHP2, sélectif et disponible par voie orale avec un IC50 de 70 nM.

SHP099 is a potent, selective, orally available SHP2 inhibitor with an IC50 of 70 nM.

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

SHP099 Chemical Structure

SHP099 Chemical Structure

CAS No. : 1801747-42-1

Size Price Stock Quantity
Free Sample (0.1 - 0.5 mg)   Apply Now  
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 70 In-stock
Solution
10 mM * 1 mL in DMSO USD 70 In-stock
Solid
5 mg USD 90 In-stock
10 mg USD 150 In-stock
50 mg USD 450 In-stock
100 mg USD 640 In-stock
200 mg   Get quote  
500 mg   Get quote  

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This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 55 publication(s) in Google Scholar

Other Forms of SHP099:

Top Publications Citing Use of Products

51 Publications Citing Use of MCE SHP099

WB

    SHP099 purchased from MedChemExpress. Usage Cited in: Cancer Discov. 2018 Oct;8(10):1237-1249.  [Abstract]

    Immunoblots of whole cell lysates or GST-RBD-precipitated (RAS-GTP, KRASGTP and NRAS-GTP) lysates from PDAC cells treated with DMSO, SHP099 10 μM, AZD6244 1 μM, or both drugs for the times indicated.

    SHP099 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2019 Apr 1;10(1):1473.  [Abstract]

    SHP099 inhibits IRS1-AP2 interaction in primary hepatocytes.

    SHP099 purchased from MedChemExpress. Usage Cited in: Hepatology. 2018 Jul;68(1):333-348.  [Abstract]

    Primary human HSCs are treated with SHP099 for 1 hour. PDGF-BB is added and cells are cultured for 12 additional hours. Whole cell lysates and EVs are examined by WB (n=6).

    SHP099 purchased from MedChemExpress. Usage Cited in: Open Biol. 2017 May;7(5). pii: 170066.  [Abstract]

    Comparing the effects of SHP2 degradation and allosteric inhibition on Ras/MAPK signalling. (a) Human U2OS, A549, K-562 and MDA-MB-468 cells are treated with DMSO control or 1, 5 and 10 µM SHP099 for 2 h prior to lysis. Extracts (10 µg protein) are resolved by SDS-PAGE and transferred to nitrocellulose membranes, which are subjected to western blotting with the indicated antibodies. (b) Uninfected U2OS cells (WT) or cells infected with retroviruses encoding VHL, aCS3 and VHL-aCS3 are treated wit
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    SHP099 is a potent, selective, orally available SHP2 inhibitor with an IC50 of 70 nM[1].

    IC50 & Target

    IC50: 70 nM (SHP2)[1]

    In Vitro

    The X-ray co-crystal for SHP099 with SHP2 reveals a new interaction with the basic amine and the Phe113 backbone carbonyl. SHP099 shows inhibition of cell proliferation (KYSE-520 model) with an IC50 of 1.4 μM. SHP099 shows high solubility and high permeability with no apparent efflux in Caco-2 cells[1]. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells[2].

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

    In Vivo

    After a single dose of 30 and 100 mg/kg (red and blue lines, respectively), dose-dependent exposure and modulation of the pharmacodynamic marker p-ERK is observed in the xenografts. A daily oral dose of 10 or 30 mg/kg yield 19% and 61% tumor growth inhibition, respectively. Tumor stasis is achieved at 100 mg/kg[1].

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

    Molecular Weight

    352.26

    Formula

    C16H19Cl2N5

    CAS No.
    Appearance

    Solid

    Color

    Light yellow to yellow

    SMILES

    NC1=NC(N2CCC(C)(N)CC2)=CN=C1C3=CC=CC(Cl)=C3Cl

    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 : 12 mg/mL (34.07 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    H2O : < 0.1 mg/mL (insoluble)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.8388 mL 14.1941 mL 28.3881 mL
    5 mM 0.5678 mL 2.8388 mL 5.6776 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. 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)

    Mass
    =
    Concentration
    ×
    Volume
    ×
    Molecular Weight *

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

    ×
    Volume (final)

    V2

    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: ≥ 1.2 mg/mL (3.41 mM); Clear solution

      This protocol yields a clear solution of ≥ 1.2 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.0 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: ≥ 1.2 mg/mL (3.41 mM); Clear solution

      This protocol yields a clear solution of ≥ 1.2 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.0 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.

    For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
    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:  0.5% CMC-Na/saline water

      Solubility: 10 mg/mL (28.39 mM); Suspended solution; Need ultrasonic

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    +
    %
    Tween-80 +
    %
    Saline
    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: 99.80%

    References
    Kinase Assay
    [1]

    The inhibition of SHP2 from the tested compounds (SHP099) concentrations varying from 0.003-100 μM is monitored using an assay in which 0.5 nM of SHP2 is incubated with of 0.5 μM of peptide IRS1_pY1172(dPEG8)pY1222. After 30-60 minutes incubation at the surrogate substrate, DiFMUP is added to the reaction and incubated at 25 °C for 30 minutes. The reaction is then quenched by the addition of 5 μL of a 160 μM solution of bpV(Phen). The fluorescence signal is monitored using a microplate reader using excitation and emission wavelengths of 340 nm and 450 nm, respectively[1].

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

    Cell Assay
    [1]

    Cells are plated onto 96-well plates in 100 μL medium. SHP099 with various concentrations (1.25, 2.5, 5, 10, 20 μM) are added 24 h after cell plating. At day 5, 50 μL Celltiter-Glo reagent is added, and the luminescent signal is determined[1].

    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. 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 2.8388 mL 14.1941 mL 28.3881 mL 70.9703 mL
    5 mM 0.5678 mL 2.8388 mL 5.6776 mL 14.1941 mL
    10 mM 0.2839 mL 1.4194 mL 2.8388 mL 7.0970 mL
    15 mM 0.1893 mL 0.9463 mL 1.8925 mL 4.7314 mL
    20 mM 0.1419 mL 0.7097 mL 1.4194 mL 3.5485 mL
    25 mM 0.1136 mL 0.5678 mL 1.1355 mL 2.8388 mL
    30 mM 0.0946 mL 0.4731 mL 0.9463 mL 2.3657 mL
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    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.

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    Product Name:
    SHP099
    Cat. No.:
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