PIM447

Alias: PIM447; PIM-447; PIM 447; LGH-447; LGH 447; LGH447
Cat No.:V2728 Purity: ≥98%
PIM447 (also known as LGH447)is a novel and potent pan-PIM (proviral insertion site of Moloney murine leukemia)kinase inhibitor with Ki values of 6 pM, 18 pM, 9 pM for PIM1, PIM2, PIM3 respectively.
PIM447 Chemical Structure CAS No.: 1210608-43-7
Product category: Pim
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
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25mg
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Other Forms of PIM447:

  • PIM447 dihydrochloride
Official Supplier of:
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Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

PIM447 (also known as LGH447) is a novel and potent pan-PIM (proviral insertion site of Moloney murine leukemia) kinase inhibitor with Ki values of 6 pM, 18 pM, 9 pM for PIM1, PIM2, PIM3 respectively. It also inhibits GSK3β, PKN1, and PKCτ, but at a significantly lower potency with IC50 between 1 and 5 μM (>105-fold differential relative to the Ki on PIMs). PIM447 is cytotoxic for myeloma cells due to cell cycle disruption and induction of apoptosis mediated by a decrease in phospho-Bad (Ser112) and c-Myc levels and the inhibition of mTORC1 pathway. PIM447 is currently undergoing several clinical trials.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
On multiple myeloma (MM) cells, PIM447 (0.05–10 μM; 24-72 hours) exhibits an antiproliferative effect[2]. Apoptosis is induced by PIM447 (10 μM; 6-24 hours)[2]. In the two cell lines (MM1S and OPM-2 cells), PIM447 (0.1–10 μM; 48 hours) reduces the proliferative phases (S and G2–M) of the cell cycle and raises the percentage of cells in the G0-G1 phase[2].
ln Vivo
Tumor burden is decreased by PIM447 (100 mg/kg; po; 5 times per week)[2].
Cell Assay
Cell Viability Assay[2]
Cell Types: MM1S, MM1R, RPMI-8226, MM144, U266, NCI-H929, OPM-2, RPMI-LR5, U266-Dox4, and U266-LR7 cells
Tested Concentrations: 0.05, 0.1, 0.5, 1, 5, 10 μM
Incubation Duration: 24, 48, 72 hrs (hours)
Experimental Results: Sensitive cell lines with IC50 values at 48 hrs (hours) 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 hrs (hours) >7 μmol/L (OPM-2, RPMI-LR5, U266-Dox4, and U266-LR7).

Western Blot Analysis[2]
Cell Types: MM1S cells
Tested Concentrations: 10 μM
Incubation Duration: 6, 12, 24 hrs (hours)
Experimental Results: Promoted the cleavage of initiator caspases, such as caspases 8 and 9, and also the cleavage of the effector caspases 3 and 7, together with PARP cleavage.
Animal Protocol
Animal/Disease Models: 6weeks old female NOD-SCID-IL-2Rγ−/− (NSG) mice (bearing RPMI-8226 -luc cells)[2]
Doses: 100 mg/kg
Route of Administration: po; 5 times for a week
Experimental Results: Clearly controlled tumor progression as measured by bioluminescence.
References
[1]. Burger MT, et al. Identification of N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase Inhibito
[2]. Paíno T et al. The novel pan-PIM kinase inhibitor, PIM447, displays dual anti-myeloma and bone protective effects, and potently synergizes with current standards of care. Clin Cancer Res. 2016 Jul 20.
[3]. Peters TL et al. Control of translational activation by PIM kinase in activated B-cell diffuse large B-cell lymphoma confers sensitivity to inhibition by PIM447. Oncotarget. 2016 Aug 20
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C24H23F3N4O.HCL
Molecular Weight
476.92
CAS #
1210608-43-7
SMILES
O=C(NC1=C([ C@H]2C[C@@H](N)C[C@@H](C)C2)C=CN=C1)C3=NC(C4=C(F)C=CC=C4F)=C(F)C=C3
Synonyms
PIM447; PIM-447; PIM 447; LGH-447; LGH 447; LGH447
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 88 mg/mL (184.5 mM)
Water:<1 mg/mL
Ethanol:88 mg/mL (184.5 mM)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.0968 mL 10.4839 mL 20.9679 mL
5 mM 0.4194 mL 2.0968 mL 4.1936 mL
10 mM 0.2097 mL 1.0484 mL 2.0968 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Biological Data
  • PIM447
    Antitumor activity and tolerability of single agent compound 8 and compound 8 in combination with Ara-C in KG-1 acute myeloid leukemia subcutaneous mouse tumor model.J Med Chem.2015 Nov 12;58(21):8373-86

  • PIM447


    PIM447
    In vitro pS6RP target modulation by compound 8 in KG-1 acute myeloid leukemia cell line.J Med Chem.2015 Nov 12;58(21):8373-86
  • PIM447
    Single dose pS6RP target modulation and plasma exposure of compound 8 in KG-1 acute myeloid leukemia subcutaneous mouse tumor model.J Med Chem.2015 Nov 12;58(21):8373-86
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