PF-03084014 (PF-3084014)CAS号: 1290543-63-3分子式: C27H41F2N5O分子量: 489.64描述纯度储存/保存方法别名外观可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)
产品描述 | |
描述 |
PF-03084014 (PF-3084014) is a selective gamma-secretase inhibitor with IC50 of 6.2 nM in a cell-free assay. Phase 2. |
纯度 |
98%
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储存/保存方法 |
Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.
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基本信息 | |
别名 |
Nirogacestat
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外观 |
white to beige powder
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可溶性/溶解性 |
DMSO : 90 mg/mL (183.8 mM)
Ethanol : 90 mg/mL (183.8 mM) |
生物活性 | |
靶点 |
γ-secretase
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In vitro(体外研究) |
PF-03084014 inhibits Notch receptor cleavage in cellular assays using HPB-ALL cells that harbor mutations in both the heterodimerization and PEST domains in Notch1with IC50 of 13.3 nM. PF-03084014 downregulates Notch target genes Hes-1, and cMyc expression in HPB-ALL cells with IC50 of PF-03084014 reduces proliferation of HUVECs with IC50 of 0.5 μM, and decreases the lumen formation with an IC50 value of 50 nM. PF-03084014 (1 μM) has no antiproliferative effect in MX1 cells; however, it inhibits migration by 95%.
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In vivo(体内研究) |
PF-03084014 orally administrated in a single dose of 200 mg/kg, causes maximal NICD inhibition for ∼80% in xenograft HPB-ALL tumors. PF-03084014 shows robust antitumor activity in this mode with a maximal tumor growth inhibition of ∼ 92% at dose of 150 mg/kg, accompanied by a significant reduction of NICD/Notch1, tumor mitotic index (Ki67), and apoptosis (activated caspase-3) staining. PF-03084014 (120 mg/kg) induces apoptosis, antiproliferation, reduces tumor cell self-renewal ability, impaires tumor vasculature, and decreases metastasis activity in breast cancer HCC1599 tumor-bearing mice. PF-03084014 treatment displays significant antitumor activity in various types of the breast xenograft models with TGI value of at least 50%.
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分子结构图