CAS NO: | 1290543-63-3 |
包装 | 价格(元) |
10 mM * 1 mL in DMSO | 电议 |
5mg | 电议 |
10mg | 电议 |
50mg | 电议 |
100mg | 电议 |
200mg | 电议 |
500mg | 电议 |
生物活性 | Nirogacestat (PF-3084014) is a reversible, orally bioavailable, noncompetitive, and selectiveγ-secretaseinhibitor with anIC50of 6.2 nM. Inhibition ofNotchsignaling by Nirogacestat while minimizing gastrointestinal toxicity presents a promising approach for research ofNotchreceptor-dependent cancers[1]. | ||||||||||||||||
IC50& Target | IC50: 6.2 nM (γ-secretase)[1] | ||||||||||||||||
体外研究 (In Vitro) | The IC50of 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 IC50is 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[1]. | ||||||||||||||||
体内研究 (In Vivo) | 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[1]. | ||||||||||||||||
Clinical Trial | |||||||||||||||||
分子量 | 489.64 | ||||||||||||||||
性状 | Solid | ||||||||||||||||
Formula | C27H41F2N5O | ||||||||||||||||
CAS 号 | 1290543-63-3 | ||||||||||||||||
运输条件 | Room temperature in continental US; may vary elsewhere. | ||||||||||||||||
储存方式 |
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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℃)(insoluble) 配制储备液
* 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。 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
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