[CAS NO. 1421438-81-4] Crenigacestat (LY3039478)
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PRODUCTS SPECIFICATIONS [1421438-81-4]
Distributor
Catalog
SLK-S7169
Brand
Selleck
CAS
1421438-81-4
DESCRIPTION [1421438-81-4]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 464.44 |
| Molecular Formula | C22H23F3N4O4 |
| SMILES | - |
For research use only.
Storage
3 years,-20°C,powder
1 years,-80°C,in solvent
1 years,-80°C,in solvent
Shipping
Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)
Preparing Stock Solutions
| 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1531 mL | 10.7657 mL | 21.5313 mL |
| 5 mM | 0.4306 mL | 2.1531 mL | 4.3063 mL |
| 10 mM | 0.2153 mL | 1.0766 mL | 2.1531 mL |
| 50 mM | 0.0431 mL | 0.2153 mL | 0.4306 mL |
Description
Crenigacestat (LY3039478) is an oral and inhibitor with IC50 of 0.41 nM for Notch.
Targets
| Notch [1] |
| ~1 nM |
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. 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.
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. 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. 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.
References
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