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PIM447 (LGH447)
Catalog No.S7985
For research use only.
PIM447 (LGH447) is a novel pan-PIM 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 induces apoptosis.
CAS No. 1210608-43-7(freebase)
Selleck's PIM447 (LGH447) has been cited by 13 publications
Purity & Quality Control
Choose Selective Pim Inhibitors
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Biological Activity
| Description | PIM447 (LGH447) is a novel pan-PIM 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 induces apoptosis. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Targets |
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| In vitro |
The kinase selectivity of PIM447 is first determined in biochemical assays for a panel of 68 diverse protein kinases that included PIM2 as well as 9 lipid kinases. In this panel, only PIM2 is significantly inhibited by PIM447 with an IC50 of <0.003 μM, the lowest sensitivity range for the assay. PIM447 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). The biochemical IC50 for all other kinases tested in this panel is >9 μM. In follow-up cellular assays of GSK3β inhibition, PIM447 is tested up to 20 μM and is not active[1]. 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 also inhibits in vitro osteoclast formation and resorption, downregulates key molecules involved in these processes, and partially disrupts the F-actin ring, while increasing osteoblast activity and mineralization[2]. |
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| Cell Data |
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| In vivo | Low to moderate in vivo CL is observed for PIM447 across species, as CL values of 20, 28, and 8 mL/min/kg are observed in mouse, rat, and dog, respectively. The volume of distribution is consistently large across species, with Vss of 5.3, 6.4, and 3.6 L/kg observed in mouse, rat, and dog, respectively. Additionally, PIM447 exhibits high oral bioavailability across species, as 84%, 70%, and 71% is observed in mouse, rat, and dog, respectively. The stability of PIM447 in human plasma is high, >90% after a 3 h incubation, and the human plasma protein binding of PIM447 is 95%. With the combination of potent in vitro activity and low to moderate CL, PIM447 demonstrates in vivo target modulation (pS6RP), single agent antitumor activity in a KG-1 AML mouse xenograft model, and druglike properties suitable for development[1]. PIM447 significantly reduces the tumor burden and prevents tumor-associated bone loss in a disseminated murine model of human myeloma[2]. |
Protocol (from reference)
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Solubility (25°C)
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Chemical Information
| Molecular Weight | 476.92 | ||
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| Formula | C24H23F3N4O.HCl |
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| CAS No. | 1210608-43-7(freebase) | ||
| Storage | 3 years | -20°C | powder |
| 2 years | -80°C | in solvent | |
| Smiles | CC1CC(CC(C1)N)C2=C(C=NC=C2)NC(=O)C3=NC(=C(C=C3)F)C4=C(C=CC=C4F)F | ||
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Clinical Trial Information
| NCT Number | Recruitment | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|---|
| NCT02160951 | Completed | Drug: LGH447 | Multiple Myeloma | Novartis Pharmaceuticals|Novartis | September 2014 | Phase 1 |
| NCT02078609 | Completed | Drug: LGH447|Drug: LGH447 + midostaurin | AML and High Risk MDS | Novartis Pharmaceuticals|Novartis | March 20 2014 | Phase 1 |
| NCT01456689 | Completed | Drug: LGH447|Drug: midazolam | Multiple Myeloma | Novartis Pharmaceuticals|Novartis | April 25 2012 | Phase 1 |
(data from https://clinicaltrials.gov, updated on 2022-08-01)
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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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