| 货号 | 规格 | 价格 | 上海 | 北京 | 珠海 | 重庆 | 武汉 | 购买数量 |
|---|---|---|---|---|---|---|---|---|
S84048-1mg |
≥99% | ￥1000.00 |
货期：3-5天 | - | - | - | - |
|
S84048-5mg |
≥99% | ￥2470.00 |
货期：3-5天 | - | - | - | - |
|
S84048-10mg |
≥99% | ￥3960.00 |
货期：3-5天 | - | - | - | - |
|
| 产品描述： | 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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| 靶点： | Ki: 6 pM (PIM1); 18 pM (PIM1); 9 pM (PIM3);Others | ||||||||||||||||||||
| 体外研究： | 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). 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 lin | ||||||||||||||||||||
| 体内研究： | 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. | ||||||||||||||||||||
| 参考文献： | 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. 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. 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 | ||||||||||||||||||||
| 溶解性： | Soluble in DMSO、H2O | ||||||||||||||||||||
| 保存条件： | -20℃ | ||||||||||||||||||||
| 配置溶液浓度参考： |
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| 注意： | 部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
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