PIM447 DIHYDROCHLORIDE
PIM447 DIHYDROCHLORIDE 用途与合成方法
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. |
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 价格(试剂级)
| 更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
|---|---|---|---|---|---|
| 2024-11-08 | HY-19322B | PIM447 DIHYDROCHLORIDE | 1820565-69-2 | 1mg | 1350 |
| 2024-11-08 | HY-19322B | PIM447 DIHYDROCHLORIDE | 1820565-69-2 | 5mg | 3000 |
