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。
| 生物活性 | PF-5274857 hydrochloride is a potent, selective, orally active and brain-penetrant antagonist ofSmo, with anIC50of 5.8 nM andKiof 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 IC50of 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].
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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].
| 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 IC50of 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. |
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| 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. |
