PIM-447 dihydrochloride LGH447 dihydrochloride|cas:1820565-69-2|西域试剂

PIM-447 dihydrochloride LGH447 dihydrochloride,99.27%

产品编号：Bellancom-19322B| CAS NO：1820565-69-2| 分子式：C₂₄H₂₅Cl₂F₃N₄O| 分子量：513.38

本网站销售的所有产品仅用于工业应用或者科学研究等非医疗目的,不可用于人类或动物的临床诊断或者治疗,非药用,非食用，

货号	价格	库存与货期
Bellancom-19322B	￥1350.00	杭州北京（现货）
Bellancom-19322B	￥3700.00	杭州北京（现货）
Bellancom-19322B	￥6300.00	杭州北京（现货）
Bellancom-19322B	￥19500.00	杭州北京（现货）
Bellancom-19322B	￥28500.00	杭州北京（现货）

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PIM-447 dihydrochloride 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 K_i 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-PIM kinase inhibitor, with K_i 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.

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

性状

Solid

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°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 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-CD in 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 μL 20% 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