Nirogacestat PF-3084014; PF-03084014|cas:1290543-63-3|西域试剂

Nirogacestat PF-3084014; PF-03084014,98.76%

产品编号：Bellancom-15185| CAS NO：1290543-63-3| 分子式：C₂₇H₄₁F₂N₅O| 分子量：489.64

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-15185	￥990.00	杭州北京（现货）
Bellancom-15185	￥1650.00	杭州北京（现货）
Bellancom-15185	￥6600.00	杭州北京（现货）
Bellancom-15185	￥11000.00	杭州北京（现货）

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Nirogacestat PF-3084014; PF-03084014

产品介绍

Nirogacestat (PF-3084014) 是一种有效的，具有口服活性的，可逆的非竞争性的选择性的 γ-secretase 抑制剂，IC₅₀ 为 6.2 nM。Nirogacestat 抑制 Notch 信号通路，同时最小化胃肠道毒性。可用于研究 Notch 受体依赖性肿瘤。

生物活性

Nirogacestat (PF-3084014) is a reversible, orally bioavailable, noncompetitive, and selective γ-secretase inhibitor with an IC₅₀ of 6.2 nM. Inhibition of Notch signaling by Nirogacestat while minimizing gastrointestinal toxicity presents a promising approach for research of Notch receptor-dependent cancers.

体外研究

The IC₅₀ of Nirogacestat (PF-03084014) for γ-secretase enzyme inhibition in cell-free assay for Aβ production using detergent solubilized membranes derived from HeLa cells is determined to be 6.2 nM. When tested for inhibition of Notch receptor cleavage in cellular assays using HPB-ALL cells that harbor mutations in both the heterodimerization and PEST domains in Notch1, the cell IC₅₀ is determined to be 13.3 nM. Nirogacestat (PF-03084014) causes a significant increase in caspase-3 activities in HPB-ALL and TALL-1 cells as well as an induction of cleaved PARP and cleaved caspase-3 after a 7-day treatment.

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

体内研究

Nirogacestat (PF-03084014) shows robust antitumor activity in this model on 14-day twice daily dosing. Tumor growth inhibition is dose dependent, with maximal tumor growth inhibition of ~92% obtained at high dose levels (150 mg/kg). In tumor growth inhibition studies where mice receive repetitive twice daily dosing for more than a week, Nirogacestat (PF-03084014) is well tolerated at dose levels below 100 mg/kg as no significant weight loss, morbidity, or mortality is observed. When the dose is increased to 150 mg/kg, however, mice have diarrhea and show weight loss (10-15%) approximately 10 days after compound administration. The body weight of treated animals usually returns to normal if dosing holidays are given, suggesting that the toxicity of Nirogacestat (PF-03084014) is reversible.

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

体内研究

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

性状

Solid

溶解性数据

In Vitro:

DMSO : 28.57 mg/mL (58.35 mM; Need ultrasonic)

H₂O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.0423 mL	10.2116 mL	20.4232 mL
5 mM	0.4085 mL	2.0423 mL	4.0846 mL
10 mM	0.2042 mL	1.0212 mL	2.0423 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。-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 (5.11 mM); Suspended solution; Need ultrasonic and warming

此方案可获得 2.5 mg/mL (5.11 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。
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 (5.11 mM); Suspended solution; Need ultrasonic

此方案可获得 2.5 mg/mL (5.11 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。
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
3.

请依序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (5.11 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (5.11 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
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玉米油中，混合均匀。
4.

请依序添加每种溶剂： 5% DMSO 40% PEG300 5% Tween-80 50% saline
Solubility: 1.43 mg/mL (2.92 mM); Suspended solution; Need ultrasonic