PIM447 DIHYDROCHLORIDE
PIM-447 (dihydrochloride)
CAS: 1820565-69-2
Molecular Formula: C24H23F3N4O
PIM447 DIHYDROCHLORIDE - Names and Identifiers
PIM447 DIHYDROCHLORIDE - Physico-chemical Properties
| Molecular Formula | C24H23F3N4O |
| Molar Mass | 440.4608296 |
| Solubility | DMSO: ≥ 46.7 mg/mL |
| Storage Condition | -20℃ |
| In vitro study | PIM-447(0.05-10 µM; 24, 48 and 72 hours)has inhibitory effects in MM cells, it against sensitive cell lines with IC 50 values ranging from 0.2 to 3.3 µM (MM1S, MM1R, RPMI-8226, MM144, U266 and NCI-H929) and less sensitive cell lines with IC 50 values at 48 h >7 µM (OPM-2,RPMI-LR5, U266-Dox4 and U266-LR7).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.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.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. Cell Viability Assay 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 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 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 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 study | 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. Animal Model: RPMI-8226-luc cells are injected intravenously into 6-week-old female NODSCID-IL-2Rγ -/- (NSG) mice 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. |
PIM447 DIHYDROCHLORIDE - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 1.948 ml | 9.739 ml | 19.479 ml |
| 5 mM | 0.39 ml | 1.948 ml | 3.896 ml |
| 10 mM | 0.195 ml | 0.974 ml | 1.948 ml |
| 5 mM | 0.039 ml | 0.195 ml | 0.39 ml |
Last Update：2024-01-02 23:10:35
PIM447 DIHYDROCHLORIDE - Reference Information
| biological activity | PIM447 dihydrochloride (LGH447 dihydrochloride) is an effective, oral and selective pan-PIM kinase inhibitor with Ki values of 6, 18 and 9 pM for PIM1, PIM2 and PIM3 respectively. PIM447 dihydrochloride has dual antitumor and osteoprotective effects. PIM447 dihydrochloride induce apoptosis. |
| in vitro study | PIM-447(0.05-10 m; 24, 48 and 72 hours)has inhibitory effects in MM cells, it against sensitive cell lines with IC 50 values ranging from 0.2 to 3.3 m (MM1S, MM1R, RPMI-8226, MM144, u266 and NCI-H929) and less sensitive cell lines with IC 50 values at 48 h >7 m (OPM-2,RPMI-LR5, U266-Dox4 and U266-LR7). 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.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.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. Cell Viability Assay 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 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 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 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. |
| 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 Sensitive MM cell lines: MM1S, NCI-H929 and RPMI-8226 cells Less sensitive MM cell lines: OPM-2 and RPMI-LR5 cells Sensitive MM cell lines: MM1S, NCI-H929 and RPMI-8226 cells MM1S, OPM-2 cells |
| Concentration: | 0.05-10 µM 0.05-10 µM 0.05-10 µM 0.1, 0.5 or 1 µM |
| Incubation Time: | 24, 48 and 72 hours 24, 48 and 72 hours 24, 48 hours 48 hours |
| Result: | Was cytotoxic for MM cells (PIM kinases high expressed). Induced cell apoptosis at higer doses, had no effects at 0.1-1 uM. Increased the cleavage of the effector caspases 3 and 7, and the PARP cleavage. Increased the cleavage of the effector caspases 3 and 7, and the PARP cleavage. 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. |
| in vivo research | PIM447 (oral gavage; 100 mg/kg; 5 times/week) clearly controlls tumor progression and the series levels of hIgλ secreted by RPMI-8226-luc cells in mouse model of bone marrow-disseminated human multiple myeloma. Animal Model: RPMI-8226-luc cells are injected intravenously into 6-week-old female NODSCID-IL-2Rγ -/- (NSG) MICE Dosage: 100 mg/kg Administration: oral gavage; 100 mg/kg; 5 times/week result: waswell 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. |
| Animal Model: | RPMI-8226-luc cells are injected intravenously into 6-week-old female NODSCID-IL-2Rγ -/- (NSG) mice |
| Dosage: | 100 mg/kg |
| Administration: | oral gavage; 100 mg/kg; 5 times/week |
Last Update：2024-04-09 19:05:04
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Product Name: PIM-447 (dihydrochloride) Visit Supplier Webpage Request for quotation
CAS: 1820565-69-2
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 1820565-69-2
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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