您好,欢迎来到试剂信息网! [登录] [免费注册]
试剂信息网
位置:首页 > 产品库 > PIM-447 dihydrochloride
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
PIM-447 dihydrochloride
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
PIM-447 dihydrochloride图片
CAS NO:1820565-69-2
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
1mg电议
5mg电议
10mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品名称
LGH447 dihydrochloride
产品介绍
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。
生物活性

PIM447 dihydrochloride (LGH447 dihydrochloride) is a potent, orally available, and selective pan-PIMkinase inhibitor, withKivalues of 6, 18, and 9 pM forPIM1,PIM2, andPIM3, respectively. PIM447 dihydrochloride displays dual antimyeloma and bone-protective effects. PIM447 dihydrochloride inducesapoptosis[1][2].

IC50& Target

Ki: 6 pM (PIM1); 18 pM (PIM1); 9 pM (PIM3)[1]

体外研究
(In Vitro)

PIM-447 (0.05-10 μM; 24, 48 and 72 hours) has inhibitory effects in MM cells, it against sensitive cell lines with IC50values ranging from 0.2 to 3.3 μM (MM1S, MM1R, RPMI-8226, MM144, U266 and NCI-H929) and less sensitive cell lines with IC50values at 48 h >7 μM (OPM-2, RPMI-LR5, U266-Dox4 and U266-LR7)[1].
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[1].
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[1].
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[1].

Cell Viability Assay[1]

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[1]

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[1]

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[1]

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.
体内研究
(In Vivo)

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[1].

Animal Model:RPMI-8226-luc cells are injected intravenously into 6-week-old female NODSCID-IL-2Rγ-/-(NSG) mice[1]
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.
Clinical Trial
分子量

513.38

性状

Solid

Formula

C24H25Cl2F3N4O

CAS 号

1820565-69-2

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

溶解性数据
In Vitro: 

H2O : 50 mg/mL(97.39 mM;Need ultrasonic)

DMSO : ≥ 46.7 mg/mL(90.97 mM)

*"≥" means soluble, but saturation unknown.

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM1.9479 mL9.7394 mL19.4787 mL
5 mM0.3896 mL1.9479 mL3.8957 mL
10 mM0.1948 mL0.9739 mL1.9479 mL
*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40%PEG300   5%Tween-80   45% saline

    Solubility: ≥ 2.5 mg/mL (4.87 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (4.87 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH2O 中,得到澄清透明的生理盐水溶液
  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20%SBE-β-CDin saline)

    Solubility: ≥ 2.5 mg/mL (4.87 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (4.87 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
*以上所有助溶剂都可在本网站选购。