您好，欢迎来到半岛电竞官方网址 ！ [ 登录] [ 免费注册]
半岛电竞官方网址
发布求购
位置： 首页> 半岛bd体育手机客户端 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
本半岛bd体育手机客户端 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

半岛bd体育手机客户端 名称
LGH447 dihydrochloride
半岛bd体育手机客户端 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 mg 5 mg 10 mg
1 mM 1.9479 mL 9.7394 mL 19.4787 mL
5 mM 0.3896 mL 1.9479 mL 3.8957 mL
10 mM 0.1948 mL 0.9739 mL 1.9479 mL
*

请根据半岛bd体育手机客户端 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半岛bd体育手机客户端 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% DMSO40%PEG3005%Tween-8045% 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% DMSO90% (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。
Baidu
map