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  • 化合物 PF03084014|T6935|TargetMol

化合物 PF03084014|T6935|TargetMol

Nirogacestat
1290543-63-3
366 1mg 起订
822 5mg 起订
1370 10mg 起订
上海 更新日期:2024-12-12

TargetMol中国(陶术生物)

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联系人:邵小姐
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邮箱:marketing@tsbiochem.com

产品详情:

中文名称:
化合物 PF03084014
英文名称:
Nirogacestat
CAS号:
1290543-63-3
品牌:
TargetMol
产地:
美国
保存条件:
Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.
纯度规格:
99.77%
产品类别:
抑制剂
货号:
T6935

Product Introduction

Bioactivity

名称Nirogacestat
描述Nirogacestat (PF 03084014) is a specific γ-secretase inhibitor (IC50: 6.2 nM, in a cell-free assay).
细胞实验Cell lines: Human T-ALL cell lines HPB-ALL. Concentrations: ~1 μM. Method: Cells are seeded in 96-well plates at 10,000 cells/well in growth media supplemented with 10% fetal bovine serum.Serial dilutions of PF-03084014 are done in DMSO,appropriate controls or designated concentrations of PF-03084014 are added to each well,and cells are incubated at 37℃ for 7 days (final DMSO content 0.1%).Resazurin at a final concentration of 0.1 mg/mL is added to the cells and plates are incubated for 2 to 4 hours.Fluorescent signals are read as emission at 590 nm after excitation at 560 nm.
激酶实验γ-secretase assay:A DNA fragment encoding amino acids 596 - 695 of the 695-aa isoform of APP (APP695) and the Flag sequence (DYKDDDDK) at the C terminus is generated by PCR amplification with suitably designed oligonucleotides and the APP695 cDNA. The Met that serves as the translation start site is residue 596 of APP695 (the P1 residue with respect to theβ-secretase cleavage site). This DNA fragment is inserted into the prokaryotic expression vector pET2-21b. The recombinant protein, C100Flag, is overproduced in Escherichia coli [strain BL21(DE3)] and purified by Mono-Q column chromatography. C100Flag (1.7 μM) is incubated with cell membranes (0.5 mg/mL) in the presence of CHAPSO, CHAPS (3-[(3-cholamidopropyl)dim-ethylammonio]-1-propanesulfonate), or Triton X-100 (0, 0.125, 0.25, 0.5, or 1%) in buffer B (50 mM Pipes, pH 7.0y 5 mM MgCl2/5 mM CaCl2/150 mM KCl) at 37°C. The reactions are stopped by adding RIPA (150 mM NaCl/1.0% NP-40/0.5% sodium deoxycholate 0.1% SDS/50 mM Tris HCl, pH 8.0) and boiling for 5 min. The samples ae centrifuged and the supernatant solutions are assayed for the Aβ peptides by ECL. The Aβ40- and Aβ42-related products from γ-secretase-mediated processing of C100Flag possess a Met at the N terminus and are thus defined as M-Aβ40 and M-Aβ42, respectively. Likewise, supernatant solution (0.125 mg/mL) from CHAPSO-extracted HeLa cell membranes (solubilized γ-secretase) is incubated with C100Flag (1.7 μM) in buffer B containing 0.25% CHAPSO and subsequently assayed for M-Aβ40 and M-Aβ42 by using ECL.
动物实验Animal Models: Human T-cell acute lymphoblastic leukemia xenografts HPB-ALL. Formulation: 0.5% methylcellulose. Dosages: 150 mg/kg,b.i.d. Administration: p.o.
体外活性Nirogacestat抑制携带 Notch1 异二聚体化和 PEST 结构域突变的 HPB-ALL 细胞中 Notch 受体的裂解(IC50:13.3 nM)。同样,Nirogacestat分别降调 HPB-ALL 细胞内 Notch 目标基因 Hes-1(IC50<1 nM)和 cMyc 表达(IC50:10 nM)。通过诱导细胞周期停滞和凋亡,Nirogacestat抑制了一部分人类 T-ALL 细胞株(包括 HPB-ALL,DND-41,TALL-1 和 Sup-T1)的细胞生长(IC50s:30-100 nM)。此外,Nirogacestat减少了 HUVECs 的增殖(IC50:0.5 μM)并且减少了管腔形成(IC50:50 nM)。尽管 PF-03084014(1 μM)对 MX1 细胞无抗增殖作用,但它能够抑制迁移率达95%。
体内活性Nirogacestat(200 mg/kg, p.o.) 在HPB-ALL异种移植瘤中导致NICD抑制达到最大约80%。在150 mg/kg剂量下,Nirogacestat显示出强大的抗肿瘤活性,最大肿瘤生长抑制率达92%,伴随着NICD/Notch1、肿瘤有丝分裂指数(Ki67)以及凋亡(激活的caspase-3)染色显著减少。Nirogacestat(120 mg/kg) 在携带HCC1599肿瘤的乳腺癌鼠模型中诱导凋亡、抗增殖,减少肿瘤细胞自我更新能力、损害肿瘤血管并降低转移活性。在各种乳腺异种移植模型中,Nirogacestat显示出显著的抗肿瘤活性(TGI>50%)。
存储条件Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.
溶解度DMSO : 90 mg/mL (183.8 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 90 mg/mL (183.8 mM)
关键字γ-secretase | Gamma secretase | cancer | inhibit | gastrointestinal | toxicity | PF3084014 | Inhibitor | Notch | Nirogacestat | PF 3084014 | Apoptosis
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PF-3084014|||PF-03084014|||PF03084014|||PF 03084014|TargetMol

公司简介

TargetMol Chemicals Inc. 总部位于马萨诸塞州波士顿,致力于为全球生化领域科学家的研究提供专业的产品和服务。TargetMol?品牌的客户群分布于40多个国家和地区,已发展成为全球知名的化合物库和小分子化合物研究供应商。 TargetMol?可提供160多种满足不同需求的化合物库,以及多种类型的生化试剂产品,包括12000多种抑制剂、16000多种天然产物和各类多肽、抗体、生命科学试剂盒等,此外,我们还建设有CADD(计算机辅助药物设计)研究中心、药理实验室、药化合成平台三大技术中心,全方位满足客户的定制需求。 凭借我们优质的产品和服务、快速高效的全球供应链和专业的技术支持,我们将有效帮助您缩短研发周期,取得更成功的结果。

成立日期 (12年)
注册资本 566.265100万人民币
员工人数 100-500人
年营业额 ¥ 1亿以上
经营模式 贸易,工厂,试剂,定制,服务
主营行业 天然产物,生化试剂,分子生物学,分子砌块,生物技术服务

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