PIM-447 dihydrochloride
Based on 8 publication(s) in Google Scholar
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.
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- Pureté : 99.82%
- CAS No.: 1820565-69-2
- Formule: C24H25Cl2F3N4O
- Masse moléculaire:513.38
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Stockage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 1 year; -20°C, 6 months (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) PIM-447 dihydrochloride
More- Nat Commun. 2026 Feb 12;17(1):1214. [Abstract]
- Cell Chem Biol. 2024 Feb 15;31(2):326-337.e11. [Abstract]
- Blood Adv. 2024 Aug 13;8(15):3880-3892. [Abstract]
- Mol Cancer Ther. 2018 Apr;17(4):849-857. [Abstract]
- J Pathol. 2020 Sep;252(1):65-76. [Abstract]
- PLoS One. 2024 Nov 1;19(11):e0308647. [Abstract]
- bioRxiv. 2024 October 24.
- bioRxiv. 2024 Mar 28.
Customer Validation & Images
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WB
Activité biologique
Description
IC50 & Target
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PIM1 |
PIM2 |
PIM3 |
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.
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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
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Concentration:0.05-10 µM
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Incubation Time:24, 48 and 72 hours
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Result:Was cytotoxic for MM cells (PIM kinases highly expressed).
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Cell Line:Sensitive MM cell lines: MM1S, NCI-H929 and RPMI-8226 cells Less sensitive MM cell lines: OPM-2 and RPMI-LR5 cells
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Concentration:0.05-10 µM
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Incubation Time:24, 48 and 72 hours
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Result:Induced cell apoptosis at higer doses, had no effects at 0.1-1 uM.
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Cell Line:Sensitive MM cell lines: MM1S, NCI-H929 and RPMI-8226 cells
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Concentration:0.05-10 µM
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Incubation Time:24, 48 hours
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Result:Increased the cleavage of the effector caspases 3 and 7, and the PARP cleavage.
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Cell Line:MM1S, OPM-2 cells
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Concentration:0.1, 0.5 or 1 µM
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Incubation Time:48 hours
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Result:Increased the cleavage of the effector caspases 3 and 7, and the PARP cleavage.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:RPMI-8226-luc cells are injected intravenously into 6-week-old female NODSCID-IL-2Rγ-/-(NSG) mice[1]
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Dosage:100 mg/kg
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Administration:oral gavage; 100 mg/kg; 5 times/week
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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.
Chemical Information
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CAS No. 1820565-69-2
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Appearance Solid
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Masse moléculaire 513.38
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Formule C24H25Cl2F3N4O
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Color White to off-white
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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
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Synonyms
LGH447 dihydrochloride
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 1 year; -20°C, 6 months (sealed storage, away from moisture)
Publications (8)
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Journal Impact Factor
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Most Recent
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Nat Commun
Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State. [Abstract]2026 Feb 12;17(1):1214. PMID: 41680175 -
Cell Chem Biol
2024 Feb 15;31(2):326-337.e11. PMID: 38016478 -
Blood Adv
Deep PIM kinase substrate profiling reveals new rational co-therapeutic strategies for acute myeloid leukemia. [Abstract]2024 Aug 13;8(15):3880-3892. PMID: 38739710 -
Mol Cancer Ther
PIM Kinases Are a Potential Prognostic Biomarker and Therapeutic Target in Neuroblastoma. [Abstract]2018 Apr;17(4):849-857. PMID: 29440296 -
J Pathol
Anti-tumour effects of PIM kinase inhibition on progression and chemoresistance of hepatocellular carcinoma. [Abstract]2020 Sep;252(1):65-76. PMID: 32558942
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.
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PLoS One
A novel small molecule screening assay using normal human chondrocytes toward osteoarthritis drug discovery. [Abstract]2024 Nov 1;19(11):e0308647. PMID: 39485774 -
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Solvant et solubilité
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.
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 year; -20°C, 6 months (sealed storage, away from moisture). When stored at -80°C, please use it within 1 year. 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.
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 year; -20°C, 6 months (sealed storage, away from moisture). When stored at -80°C, please use it within 1 year. 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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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.
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.
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:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
Pureté et documentation
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Fiche technique (284 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
[1]. 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. [Content Brief]
[2]. 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 Inhibitor in Clinical Trials for Hematological Malignancies. J Med Chem. 2015 Nov 12;58(21):8373-86. [Content Brief]
[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 [Content Brief]
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 year; -20°C, 6 months (sealed storage, away from moisture). When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| 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.
PIM-447 dihydrochloride Related Classifications
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