PIM447 (LGH447)
PIM447
CAS: 1210608-43-7
Molecular Formula: C24H23F3N4O
PIM447 (LGH447) - Names and Identifiers
PIM447 (LGH447) - Physico-chemical Properties
| Molecular Formula | C24H23F3N4O |
| Molar Mass | 440.46 |
| Density | 1.290±0.06 g/cm3(Predicted) |
| Boling Point | 493.7±45.0 °C(Predicted) |
| Solubility | 10 mM in DMSO |
| pKa | 1.35±0.70(Predicted) |
| Storage Condition | -20℃ |
| In vitro study | Through the biochemical detection of 68 different protein kinases (including PIM2) and 9 lipid kinases, it was found that PIM447 has high specificity, among which only PIM2 can be significantly inhibited by PIM447, IC50<0.003 μm. PIM447 can also inhibit GSK3β, PKN1 and pkcτ, but the effect is weak, IC50 between 1-5 μm. The IC50 values for the other kinases tested were greater than 9 μm. In the following cell experiments, when the concentration of PIM447 is as high as 20 M, it has no activity on GSK3 beta. PIM447 is cytotoxic to myeloma cells, disrupting the cell cycle and inducing a decrease in Bad(Ser112) and c-Myc levels, thereby inducing apoptosis and inhibiting the mTORC1 pathway. PIM447 also inhibits osteoclast formation and resorption in vitro, down-regulates key molecules involved in these processes, destroys the F-actin loop, and enhances osteoblast activity and mineralization. |
| In vivo study | The clearance of PIM447 was low in all species, with clearance rates of 20, 28 and 8 mL/min/kg in mice, rats and dogs, respectively. The volume of distribution is large, with Vss of 5.3, 6.4 and 3.6 L/kg in mice, rats and dogs, respectively. PIM447 also has a high oral bioavailability of 84%, 70% and 71% in mice, rats and dogs, respectively. In human plasma, PIM447 is very stable, 90% is still present 3 hours after administration, and the plasma protein binding rate is 95%. PIM447 acts as a regulatory target (pS6RP) in vivo, has single-agent antitumor activity in a KG-1 AML mouse xenograft model, and its drug-like properties make it ideal for development. In a mouse model of disseminated human myeloma, PIM447 significantly reduced tumor burden and prevented tumor-associated osteoporosis. |
PIM447 (LGH447) - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.27 ml | 11.352 ml | 22.703 ml |
| 5 mM | 0.454 ml | 2.27 ml | 4.541 ml |
| 10 mM | 0.227 ml | 1.135 ml | 2.27 ml |
| 5 mM | 0.045 ml | 0.227 ml | 0.454 ml |
Last Update：2024-01-02 23:10:35
PIM447 (LGH447) - Reference Information
| biological activity | PIM447 (LGH447) is a novel, pan-PIM kinase inhibitor for PIM1, PIM2, the Ki values of PIM3 were 6 pM, 18 pM and 9 pM, respectively. It also inhibits GSK3β, PKN1 and PKC Tau, but with less potency, with an IC50 in the range of 1-5 μm. PIM447 can induce apoptosis. |
| Target | Value |
| Pim1 (Cell-free assay) | 6 pM(Ki) |
| Pim3 (Cell-free assay) | 9 pM(Ki) |
| Pim2 (Cell-free assay) | 18 pM(Ki) |
Last Update：2024-04-09 21:21:28
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CAS: 1210608-43-7
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Product Name: PIM447 Visit Supplier Webpage Request for quotation
CAS: 1210608-43-7
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 1210608-43-7
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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