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Synonyms | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C22H23F3N4O4 |
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分子量 | 464.44 | CAS No. | 1421438-81-4 | |
Solubility (25°C)* | 体外 | DMSO | 92 mg/mL (198.08 mM) | |
Ethanol | 92 mg/mL (198.08 mM) | |||
Water | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | Crenigacestat (LY3039478) is an oral Notch and gamma-secretase inhibitor with IC50 of 0.41 nM for Notch. |
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in vitro | LY3039478 is a novel small molecule that is an exquisitely potent inhibitor of Notch-1 intracellular domain (N1ICD) cleavage with an IC50 of ∼1nM 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]. |
in vivo | 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]. |
細胞アッセイ | 細胞株 | K07074 cells |
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濃度 | 100 nM | |
反応時間 | 24, 48, 72, 96 h | |
実験の流れ | K07074 cells were plated to 24-well plates at 105 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. |
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動物実験 | 動物モデル | Mice |
投薬量 | 8 mg/kg | |
投与方法 | oral gavage |
Data from [Data independently produced by , , Eur Rev Med Pharmacol Sci, 2018, 22(13):4121-4127]
Tolerable glycometabolic stress boosts cancer cell resilience through altered N-glycosylation and Notch signaling activation [ Cell Death Dis, 2024, 15(1):53] | PubMed: 38225221 |
Cellular senescence primes liver fibrosis regression through Notch-EZH2 [ MedComm (2020), 2023, 4(5):e346] | PubMed: 37614965 |
Cellular senescence primes liver fibrosis regression through Notch-EZH2 [ MedComm -2020), 2023, 4(5):e346] | PubMed: 37614965 |
Loss of p53 enhances the tumor-initiating potential and drug resistance of clonogenic multiple myeloma cells [ Blood Adv, 2023, 7(14):3551-3560] | PubMed: 37042949 |
Familial Alzheimer's disease-associated PSEN1 mutations affect neurodevelopment through increased Notch signaling [ Stem Cell Reports, 2023, 18(7):1516-1533] | PubMed: 37352850 |
Notch signaling regulates immunosuppressive tumor-associated macrophage function in pancreatic cancer [ bioRxiv, 2023, 2023.01.11.523584] | PubMed: 36711890 |
Notch-triggered maladaptation of liver sinusoidal endothelium aggravates nonalcoholic steatohepatitis through eNOS [ Hepatology, 2022, 10.1002/hep.32332] | PubMed: 35006626 |
CD90 is regulated by notch1 and hallmarks a more aggressive intrahepatic cholangiocarcinoma phenotype [ J Exp Clin Cancer Res, 2022, 41(1):65] | PubMed: 35172861 |
Crenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-β inhibition [ J Exp Clin Cancer Res, 2022, 41(1):331] | PubMed: 36443822 |
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] | PubMed: 34997030 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。