PF-5274857 hydrochloride

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上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

PF-5274857 hydrochloride 

PF-5274857 hydrochloride 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，Ki 值为 4.6 nM。PF-5274857 hydrochloride 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。

PF-5274857 hydrochloride

PF-5274857 hydrochloride Chemical Structure

CAS No. : 1613439-62-5

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PF-5274857 hydrochloride 的其他形式现货产品:

PF-5274857

生物活性

PF-5274857 hydrochloride is a potent, selective, orally active and brain-penetrant antagonist of Smo, with an IC50 of 5.8 nM and Ki of 4.6 nM. PF-5274857 hydrochloride has potential for research of tumor types including brain tumors and brain metastasis driven by an activated Hh pathway[1].

IC50 & Target

IC50: 5.8 nM (Smo); Ki: 4.6 nM (Smo)[1]
体外研究
(In Vitro)

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[1].
PF-5274857 shows less than 20% inhibition against a broad panel of protein kinases at 1 μM[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究
(In Vivo)

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[1].
PF-5274857 (10 mg/kg; i.h.) in the plasma is able to cross the blood-brain barrier in rats within 4 hours postdose[1].
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[1].
PF-5274857 (30 mg/kg; p.o. once daily for 34 days) increases the survival rates of primary Ptch+/− p53−/− medulloblastoma mice[1].
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 (T1/2) of 1.7±0.1 hours[1].

Shanghai Jinpan Biotech Co Ltd 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[1]
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)[1]
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 (T1/2) of 1.7±0.1 hours.

分子量

473.42

Formula

C20H26Cl2N4O3S
CAS 号

1613439-62-5
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献

  • [1]. Rohner A, et, al. Effective targeting of Hedgehog signaling in a medulloblastoma model with PF-5274857, a potent and selective Smoothened antagonist that penetrates the blood-brain barrier. Mol Cancer Ther. 2012 Jan;11(1):57-65.

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