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  2. Pim Apoptosis
  3. PIM-447 dihydrochloride

PIM-447 dihydrochloride  (Synonyms: LGH447 dihydrochloride)

Cat. No.: HY-19322B Purity: 99.94%
COA Handling Instructions

PIM447 dihydrochloride (LGH447 dihydrochloride) is a potent, orally available, and selective pan-PIM kinase inhibitor, with Ki values of 6, 18, and 9 pM for PIM1, PIM2, and PIM3, respectively. PIM447 dihydrochloride displays dual antimyeloma and bone-protective effects. PIM447 dihydrochloride induces apoptosis.

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

PIM-447 dihydrochloride Chemical Structure

PIM-447 dihydrochloride Chemical Structure

CAS No. : 1820565-69-2

Size Price Stock Quantity
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 384 In-stock
Solution
10 mM * 1 mL in DMSO USD 384 In-stock
Solid
1 mg USD 135 In-stock
5 mg USD 340 In-stock
10 mg USD 550 In-stock
50 mg USD 1800 In-stock
100 mg USD 2550 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

Based on 4 publication(s) in Google Scholar

Other Forms of PIM-447 dihydrochloride:

Top Publications Citing Use of Products

    PIM-447 dihydrochloride purchased from MedChemExpress. Usage Cited in: J Pathol. 2020 Sep;252(1):65-76.  [Abstract]

    The alteration of MAPK/ERK pathway is validated by Western blotting with tumour lysates from the animal model, as illustrated by a downregulation of pERK1/2 in the PIM447 treatment group.
    • Biological Activity

    • Purity & Documentation

    • References

    • Customer Review

    Description

    PIM447 dihydrochloride (LGH447 dihydrochloride) is a potent, orally available, and selective pan-PIM kinase inhibitor, with Ki values of 6, 18, and 9 pM for PIM1, PIM2, and PIM3, respectively. PIM447 dihydrochloride displays dual antimyeloma and bone-protective effects. PIM447 dihydrochloride induces apoptosis[1][2].

    IC50 & Target

    Ki: 6 pM (PIM1); 18 pM (PIM1); 9 pM (PIM3)[1]

    In Vitro

    PIM-447 (0.05-10 µM; 24, 48 and 72 hours) has inhibitory effects in MM cells, it against sensitive cell lines with IC50 values ranging from 0.2 to 3.3 µM (MM1S, MM1R, RPMI-8226, MM144, U266 and NCI-H929) and less sensitive cell lines with IC50 values at 48 h >7 µM (OPM-2, RPMI-LR5, U266-Dox4 and U266-LR7)[1].
    PIM-447 (0.1-10 µM; 24, 48 and 72 hours) does not induce important levels of apoptosis, when PIM447 at 5 µM, it substantially increases annexin-V levels (about 30%) in sensitive cell lines(MM1S, NCI-H929 and RPMI-8226). When PIM447 at 10 µM, it induces apoptosis in all the cell lines but to a lesser extent in OPM-2 and RPMI-LR5[1].
    PIM447 promotes the cleavage of initiator caspases, such as caspases 8 and 9, and increases the cleavage of the effector caspases 3 and 7, together with PARP cleavage in MM1S,RPMI-8226 and NCI-H929 cells[1].
    PIM447 (0.1-1 µM) increases the percentage of cells in the G0/G1 phase and decreases the proliferative phases (S and G2/M) of the cell cycle. The effects at low concentrations (0.1-1 µM) were more pronounced in MM1S cells than in OPM-2[1].

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

    Cell Viability Assay[1]

    Cell Line: Sensitive MM cell lines: MM1S, MM1R, RPMI-8226, MM144, U266 and NCI-H929 cells
    Less sensitive MM cell lines: OPM-2,RPMI-LR5, U266-Dox4 and U266-LR7cells
    Concentration: 0.05-10 µM
    Incubation Time: 24, 48 and 72 hours
    Result: Was cytotoxic for MM cells (PIM kinases highly expressed).

    Apoptosis Analysis[1]

    Cell Line: Sensitive MM cell lines: MM1S, NCI-H929 and RPMI-8226 cells
    Less sensitive MM cell lines: OPM-2 and RPMI-LR5 cells
    Concentration: 0.05-10 µM
    Incubation Time: 24, 48 and 72 hours
    Result: Induced cell apoptosis at higer doses, had no effects at 0.1-1 uM.

    Western Blot Analysis[1]

    Cell Line: Sensitive MM cell lines: MM1S, NCI-H929 and RPMI-8226 cells
    Concentration: 0.05-10 µM
    Incubation Time: 24, 48 hours
    Result: Increased the cleavage of the effector caspases 3 and 7, and the PARP cleavage.

    Cell Cycle Analysis[1]

    Cell Line: MM1S, OPM-2 cells
    Concentration: 0.1, 0.5 or 1 µM
    Incubation Time: 48 hours
    Result: Increased the cleavage of the effector caspases 3 and 7, and the PARP cleavage.
    In Vivo

    PIM447 (oral gavage; 100 mg/kg; 5 times/week) clearly controlls tumor progression and the serum levels of hIgλ secreted by RPMI-8226-luc cells in mouse model of bone marrow-disseminated human multiple myeloma[1].

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

    Animal Model: RPMI-8226-luc cells are injected intravenously into 6-week-old female NODSCID-IL-2Rγ-/-(NSG) mice[1]
    Dosage: 100 mg/kg
    Administration: oral gavage; 100 mg/kg; 5 times/week
    Result: Was well tolerated, as the body weight of mice did not decrease by more than 10%.
    Increased bone volume density and trabecular number and reduced trabecular separation relative to vehicle group.
    Clinical Trial
    Molecular Weight

    513.38

    Formula

    C24H25Cl2F3N4O

    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    O=C(C1=NC(C2=C(F)C=CC=C2F)=C(F)C=C1)NC3=C([C@H]4C[C@@H](N)C[C@@H](C)C4)C=CN=C3.Cl.Cl

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage

    4°C, sealed storage, away from moisture

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

    Solvent & Solubility
    In Vitro: 

    H2O : 50 mg/mL (97.39 mM; Need ultrasonic)

    DMSO : ≥ 46.7 mg/mL (90.97 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 1.9479 mL 9.7394 mL 19.4787 mL
    5 mM 0.3896 mL 1.9479 mL 3.8957 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, 1 years; -20°C, 6 months (sealed storage, away from moisture). When stored at -80°C, please use it within 1 years. When stored at -20°C, please use it within 6 months.

    * Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

    • 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 (4.87 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 (4.87 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

    Animal weight
    (per animal)

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    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Calculation results:
    Working solution concentration: mg/mL
    This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
    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).
    Purity & Documentation

    Purity: 99.94%

    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, 1 years; -20°C, 6 months (sealed storage, away from moisture). When stored at -80°C, please use it within 1 years. When stored at -20°C, please use it within 6 months.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO / H2O 1 mM 1.9479 mL 9.7394 mL 19.4787 mL 48.6969 mL
    5 mM 0.3896 mL 1.9479 mL 3.8957 mL 9.7394 mL
    10 mM 0.1948 mL 0.9739 mL 1.9479 mL 4.8697 mL
    15 mM 0.1299 mL 0.6493 mL 1.2986 mL 3.2465 mL
    20 mM 0.0974 mL 0.4870 mL 0.9739 mL 2.4348 mL
    25 mM 0.0779 mL 0.3896 mL 0.7791 mL 1.9479 mL
    30 mM 0.0649 mL 0.3246 mL 0.6493 mL 1.6232 mL
    40 mM 0.0487 mL 0.2435 mL 0.4870 mL 1.2174 mL
    50 mM 0.0390 mL 0.1948 mL 0.3896 mL 0.9739 mL
    60 mM 0.0325 mL 0.1623 mL 0.3246 mL 0.8116 mL
    80 mM 0.0243 mL 0.1217 mL 0.2435 mL 0.6087 mL

    * Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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    • 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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