PF-5274857|cas:1373615-35-0|西域试剂

PF-5274857,98.89%

产品编号：Bellancom-13459| CAS NO：1373615-35-0| 分子式：C₂₀H₂₅ClN₄O₃S| 分子量：436.96

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货号	价格	库存与货期
Bellancom-13459	￥1600.00	杭州北京（现货）
Bellancom-13459	￥2200.00	杭州北京（现货）
Bellancom-13459	￥9000.00	杭州北京（现货）
Bellancom-13459	￥15000.00	杭州北京（现货）

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PF-5274857

产品介绍

PF-5274857 是一种有效的、选择性的、具有口服活性和可透过血脑屏障的 Smo 拮抗剂，IC₅₀ 值为 5.8 nM，K_i 值为 4.6 nM。PF-5274857 有潜力用于包括激活的 Hh 途径驱动的脑肿瘤和脑转移在内的多种肿瘤的研究。

生物活性

PF-5274857 is a potent, selective, orally active and brain-penetrant antagonist of Smo, with an IC₅₀ of 5.8 nM and K_i of 4.6 nM. PF-5274857 has potential for research of tumor types including brain tumors and brain metastasis driven by an activated Hh pathway.

体外研究

PF-5274857 completely inhibits Shh-induced Hh pathway activity with an IC₅₀ of 2.7±1.4 nM measured by the transcriptional activity of Smo downstream gene Gli1 in MEF cells.
PF-5274857 shows less than 20% inhibition against a broad panel of protein kinases at 1 μM.

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

体内研究

PF-5274857 (1-30 mg/kg; p.o. once daily for 6 days) shows robust antitumor efficacy and correlation between PK and PD in medulloblastoma allograft mice models.
PF-5274857 (10 mg/kg; i.h.) in the plasma is able to cross the blood-brain barrier in rats within 4 hours postdose.
PF-5274857 (10-100 mg/kg; p.o. once daily for 4 days) is able to target Smo in the brain leading to the downregulation of Hh pathway activity in the brain tumor.
PF-5274857 (30 mg/kg; p.o. once daily for 34 days) increases the survival rates of primary Ptch^+/− p53^−/− medulloblastoma mice.
PF-5274857 (5-30 mg/kg; p.o.) exhibits the apparent volume of distribution of 5.6±0.5 L/kg and the half-life (T_1/2) of 1.7±0.1 hours.

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

Animal Model:	Severe combined immunodeficient (SCID)-beige mice (6-8 weeks old) are genetically engineered
Dosage:	0, 1, 5, 10, 30 mg/kg
Administration:	P.o. once daily for 6 days
Result:	Showed robust antitumor activity with an in vivo IC₅₀ of 8.9±2.6 nM.

Animal Model:	Severe combined immunodeficient (SCID)-beige mice (6-8 weeks old)
Dosage:	0, 5, 10, 30 mg/kg (Pharmacokinetic Analysis)
Administration:	A single p.o.
Result:	The apparent volume of distribution of 5.6±0.5 L/kg; the half-life (T_1/2) of 1.7±0.1 hours.

体内研究

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

Animal Model:	Severe combined immunodeficient (SCID)-beige mice (6-8 weeks old) are genetically engineered
Dosage:	0, 1, 5, 10, 30 mg/kg
Administration:	P.o. once daily for 6 days
Result:	Showed robust antitumor activity with an in vivo IC₅₀ of 8.9±2.6 nM.

Animal Model:	Severe combined immunodeficient (SCID)-beige mice (6-8 weeks old)
Dosage:	0, 5, 10, 30 mg/kg (Pharmacokinetic Analysis)
Administration:	A single p.o.
Result:	The apparent volume of distribution of 5.6±0.5 L/kg; the half-life (T_1/2) of 1.7±0.1 hours.

性状

Solid

溶解性数据

In Vitro:

DMSO : 125 mg/mL (286.07 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	2.2885 mL	11.4427 mL	22.8854 mL
5 mM	0.4577 mL	2.2885 mL	4.5771 mL
10 mM	0.2289 mL	1.1443 mL	2.2885 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: ≥ 2.08 mg/mL (4.76 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.76 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 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: ≥ 2.08 mg/mL (4.76 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.76 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 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: ≥ 2.08 mg/mL (4.76 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.76 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。