PIM447 DIHYDROCHLORIDE
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- CAS号:
- 1820565-69-2
- 英文名:
- N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide
- 英文别名:
- EOS-62253;PIM-447 2HCl;LGH-447 dihydrochloride;PIM-447 (dihydrochloride);PIM 447 dihydrochloride,PIM447 dihydrochloride;N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide dihydrochloride
- 中文名:
- PIM447 DIHYDROCHLORIDE
- 中文别名:
- 泛PIM抑制剂;化合物 T12473
- CBNumber:
- CB73143071
- 分子式:
- C24H23F3N4O
- 分子量:
- 440.4608296
- MOL File:
- 1820565-69-2.mol
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PIM447 DIHYDROCHLORIDE化学性质
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储存条件:
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Store at -20°C
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溶解度:
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Water:50.0(Max Conc. mg/mL);97.39(Max Conc. mM)
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PIM447 DIHYDROCHLORIDE性质、用途与生产工艺
PIM447 dihydrochloride (LGH447 dihydrochloride) 是一种有效的、口服的、选择性的泛 PIM 激酶抑制剂,对 PIM1、PIM2 和 PIM3 的 Ki 值分别为 6、18 和 9 pM。PIM447 dihydrochloride 具有双重抗肿瘤和骨保护作用。PIM447 dihydrochloride 诱导细胞凋亡。
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:
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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
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Concentration:
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0.05-10 µM
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Incubation Time:
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24, 48 and 72 hours
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Result:
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Was cytotoxic for MM cells (PIM kinases highly expressed).
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Apoptosis Analysis
Cell Line:
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Sensitive MM cell lines: MM1S, NCI-H929 and RPMI-8226 cells
Less sensitive MM cell lines: OPM-2 and RPMI-LR5 cells
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Concentration:
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0.05-10 µM
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Incubation Time:
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24, 48 and 72 hours
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Result:
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Induced cell apoptosis at higer doses, had no effects at 0.1-1 uM.
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Western Blot Analysis
Cell Line:
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Sensitive MM cell lines: MM1S, NCI-H929 and RPMI-8226 cells
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Concentration:
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0.05-10 µM
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Incubation Time:
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24, 48 hours
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Result:
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Increased the cleavage of the effector caspases 3 and 7, and the PARP cleavage.
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Cell Cycle Analysis
Cell Line:
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MM1S, OPM-2 cells
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Concentration:
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0.1, 0.5 or 1 µM
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Incubation Time:
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48 hours
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Result:
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Increased the cleavage of the effector caspases 3 and 7, and the PARP cleavage.
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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:
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RPMI-8226-luc cells are injected intravenously into 6-week-old female NODSCID-IL-2Rγ
-/-
(NSG) mice
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Dosage:
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100 mg/kg
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Administration:
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oral gavage; 100 mg/kg; 5 times/week
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Result:
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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.
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PIM447 DIHYDROCHLORIDE
上下游产品信息
上游原料
下游产品
更新日期 | 产品编号 | 产品名称 | CAS编号 | 包装 | 价格 |
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2024/04/30 | HY-19322B | PIM447 DIHYDROCHLORIDE PIM-447 dihydrochloride | 1820565-69-2 | 1mg | 1350元 |
2024/04/30 | HY-19322B | PIM447 DIHYDROCHLORIDE PIM-447 dihydrochloride | 1820565-69-2 | 5mg | 3000元 |
PIM447 DIHYDROCHLORIDE
生产厂家
1820565-69-2, PIM447 DIHYDROCHLORIDE 相关搜索:
- 细胞生物学试剂
- 化合物 T12473
- 泛PIM抑制剂
- 1820565-69-2
- N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide dihydrochloride
- PIM 447 dihydrochloride,PIM447 dihydrochloride
- PIM-447 2HCl
- EOS-62253
- LGH-447 dihydrochloride
- PIM-447 (dihydrochloride)