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Crenigacestat
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Crenigacestat图片
CAS NO:1421438-81-4
包装与价格:
包装价格(元)
1 mg电议
5 mg电议
10 mg电议
25 mg电议
50 mg电议
100 mg电议
1 mL*10 mM(in DMSO)电议

产品名称
LY3039478
产品介绍
CrenigaceSTAT 是一种口服具有活性的Notch和γ-secretase的抑制剂,其在多种肿瘤细胞中的IC50为 ~1nM。

产品描述

LY3039478 is an orally bioavailable Notch inhibitor with an IC50 of ~1 nM in most of the tumor cell lines tested. LY3039478 effectively inhibits mutant Notch receptor activity. In a xenograft tumor model, LY3039478 inhibited expression of Notch-regulated genes and N1ICD cleavage in the tumor microenvironment.

体外活性

LY3039478 is a novel small molecule that is an exquisitely potent inhibitor of Notch-1 intracellular domain (N1ICD) cleavage with an IC50 of ~1 nM in most of the tumor cell lines tested. LY3039478 also potently inhibits mutant Notch receptor activity[2]. Treatment with a gamma secretase inhibitor, LY3039478, significantly inhibited the growth of 2 CCRCC(Clear cell renal cell carcinoma) cell lines in a concentration dependent manner. LY3039478 treatment also led to decreased expression of Myc and Cyclin A1, two genes that were part of the NOTCH driven proliferative signature in murine and human model systems. LY3039478 treatment also led to G0/G1 cell cycle arrest in CCRCC cells[3].

体内活性

In mice, its oral bioavalability(%F) is 65%, clearance(CL)=41 mL/min/kg, VDss = 3.8 L/kg. In Rats, its oral bioavalability(%F) is 65%, CL=98 mL/min/kg, VDss=4.9 L/kg. In Dogs, its oral bioavalability (%F) is 67%, CL=3.8 mL/min/kg, VDss=1.4 L/kg[1]. In a xenograft tumor model, LY3039478 inhibited N1ICD cleavage and expression of Notch-regulated genes in the tumor microenvironment. The inhibition of Notch cleavage also resulted in the induction of apoptosis in a Notch-dependent xenograft model[2]. In immunodeficient NSG mice xenografted with 769-P CCRCC cells, LY3039478 treatment resulted in significantly increased survival and delayed tumor growth in independent cohorts of mice demonstrating in vivo efficacy in CCRCC[3].

细胞实验

K07074 cells were plated to 24-well plates at 10<sup>5</sup> cell/well. Viability of cells was assessed in quadruplicates at indicated timepoints using the CellTiter-Glo luminescent cell viability assay. To study the effect of the small molecular compounds on K07074 cell growth the compounds or DMSO were added to the growth media 24 h after seeding. The cells were incubated with inhibitors and DMSO as indicated. Cell viability was assessed as described above. Each experiment was carried out in triplicate and at least 3 independent experiments were performed. (Only for Reference)

Cas No.

1421438-81-4

分子式

C22H23F3N4O4

分子量

464.445

别名

LY3039478

储存和溶解度

H2O:<1 mgml
DMSO:34 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years