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Crenigacestat

Catalog No. T3633 CAS 1421438-81-4

Synonyms: LY3039478

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

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Crenigacestat, CAS 1421438-81-4

Pack Size	Availability	Price/USD
1 mg	In stock	$ 56.00
5 mg	In stock	$ 122.00
10 mg	In stock	$ 198.00
25 mg	In stock	$ 372.00
50 mg	In stock	Inquiry
1 mL * 10 mM (in DMSO)	In stock	$ 123.00

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Purity: 98.76%

Purity: 97.36%

Purity: 97.27%

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Description	Crenigacestat (LY3039478) is an orally bioavailable Notch inhibitor with an IC50 of ~1 nM in most of the tumor cell lines tested. Crenigacestat effectively inhibits mutant Notch receptor activity. In a xenograft tumor model, Crenigacestat inhibited expression of Notch-regulated genes and N1ICD cleavage in the tumor microenvironment.
Targets&IC50	Notch1:1 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 ～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].
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].
Cell Research	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)

Synonyms	LY3039478
Molecular Weight	464.44
Formula	C22H23F3N4O4
CAS No.	1421438-81-4

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 55 mg/mL (118.42 mM)

H2O: < 1 mg/mL (insoluble or slightly soluble)

References and Literature

1. Eli Lilly Company. The 8th SCI-RSC Symposium on Proteinase Inhibitor Design. 2013. 2. Mark H. Bender, et al. Cancer Res, 2013, 73(8 Suppl):Abstract nr 1131. 3. Bhagat TD, et al. J Biol Chem. 2017, 292(3):837-846. 4. Mäemets-Allas K, et al. Biochem Biophys Res Commun. 2016 May 20;474(1):118-25. 5. Lu B, He Y, He J, et al. Epigenetic Profiling Identifies LIF as a Super-enhancer-Controlled Regulator of Stem Cell–like Properties in Osteosarcoma[J]. Molecular Cancer Research. 2020, 18(1): 57-67.

Citations

1. Lu B, He Y, He J, et al. Epigenetic profiling identifies LIF as a super-enhancer controlled regulator of stem cell-like properties in osteosarcoma. Molecular Cancer Research. 2020, 18(1): 57-67

Related compound libraries

This product is contained In the following compound libraries：

Anti-Cancer Drug Library Inhibitor Library Drug Repurposing Compound Library Anti-Cancer Active Compound Library Anti-Cancer Clinical Compound Library Anti-Neurodegenerative Disease Compound Library Anti-Breast Cancer Compound Library Bioactive Compound Library Anti-Cancer Compound Library Anti-Colorectal Cancer Compound Library

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Keywords

Crenigacestat 1421438-81-4 Neuroscience Proteases/Proteasome Stem Cells Gamma-secretase Inhibitor γ-secretase LY 3039478 liver LY-3039478 Notch LY3039478 Gamma secretase inhibit CCRCC inhibitor

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