1. Metabolic Enzyme/Protease
  2. Phosphatase
  3. SHP099 hydrochloride

SHP099 hydrochloride 

Cat. No.: HY-100388A Purity: 99.67%
Handling Instructions

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

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

SHP099 hydrochloride Chemical Structure

SHP099 hydrochloride Chemical Structure

CAS No. : 1801747-11-4

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 72 In-stock
Estimated Time of Arrival: December 31
1 mg USD 60 In-stock
Estimated Time of Arrival: December 31
5 mg USD 84 In-stock
Estimated Time of Arrival: December 31
10 mg USD 120 In-stock
Estimated Time of Arrival: December 31
50 mg USD 288 In-stock
Estimated Time of Arrival: December 31
100 mg USD 528 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 18 publication(s) in Google Scholar

Other Forms of SHP099 hydrochloride:

Top Publications Citing Use of Products

    SHP099 hydrochloride purchased from MCE. Usage Cited in: Open Biol. 2017 May;7(5). pii: 170066.

    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

    SHP099 hydrochloride purchased from MCE. Usage Cited in: bioRxiv. April 25, 2018.

    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 hydrochloride purchased from MCE. Usage Cited in: Cancer Discov. 2018 Oct;8(10):1237-1249.

    Immunoblots of SHP2, p-ERK, ERK, p-MEK and MEK from MiaPaCa-2 cells ectopically-expressing wild-type SHP2 (WT) or an SHP099- resistant mutant (P491Q), treated as indicated.

    SHP099 hydrochloride purchased from MCE. Usage Cited in: Hepatology. 2018 Jul;68(1):333-348.

    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 hydrochloride purchased from MCE. Usage Cited in: bioRxiv. September 17, 2018.

    SHP099 inhibits IRS1-AP2 interaction in primary hepatocytes.

    SHP099 hydrochloride purchased from MCE. Usage Cited in: Nat Commun. 2019 Apr 1;10(1):1473.

    Insulin signaling in the liver from mice fed HFD for 5 weeks. The mice are administered vehicle or SHP099 for 5 days, fasted overnight, and administered vehicle or SHP099 once more. At 2 h after the last administration, the mice are injected with or without 1 U insulin via inferior vena cava. The livers are collected at the indicated time points. Lysates were prepared from these tissues and subjected to quantitative immunoblotting with the indicated antibodies.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

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

    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].

    In Vivo

    After a single doses 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].

    Molecular Weight

    388.72

    Formula

    C₁₆H₂₀Cl₃N₅

    CAS No.

    1801747-11-4

    SMILES

    NC1=NC(N2CCC(C)(N)CC2)=CN=C1C3=CC=CC(Cl)=C3Cl.[H]Cl

    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: 

    Methanol : 15 mg/mL (38.59 mM; Need ultrasonic)

    DMSO : 4.1 mg/mL (10.55 mM; Need ultrasonic and warming)

    H2O : ≥ 2.5 mg/mL (6.43 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.5725 mL 12.8627 mL 25.7255 mL
    5 mM 0.5145 mL 2.5725 mL 5.1451 mL
    10 mM 0.2573 mL 1.2863 mL 2.5725 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      SHP099 hydrochloride is resuspended in 0.6% methylcellulose, 0.5% Tween80 in 0.9% saline[3].

    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

    Purity: 99.67%

    • 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

    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:
    SHP099 hydrochloride
    Cat. No.:
    HY-100388A
    Quantity: