Crenigacestat (LY3039478) - Moligand™, 10mM in DMSO , CAS No.1421438-81-4

CAS: 1421438-81-4 Cat. No.: C408763 Molecular Weight: 464.44

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

Butanamide, N-[(1S)-2-[[(7S)-6,7-dihydro-5-(2-hydroxyethyl)-6-oxo-5H-pyrido[3,2-a][3]benzazepin-7-yl]amino]-1-methyl-2-oxoethyl]-4,4,4-trifluoro-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

Crenigacestat (LY3039478) is an oralNotchandgamma-secretaseinhibitor with IC50 of 0.41 nM for Notch.
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.
Cell Data

cell lines：

Concentrations：100 nM

Incubation Time：24, 48, 72, 96 h

Powder Purity:≥98%

Specifications

Synonyms

Butanamide, N-[(1S)-2-[[(7S)-6, 7-dihydro-5-(2-hydroxyethyl)-6-oxo-5H-pyrido[3, 2-a][3]benzazepin-7-yl]amino]-1-methyl-2-oxoethyl]-4, 4, 4-trifluoro-

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

Crenigacestat (LY3039478) is an oral Notch and gamma-secretase inhibitor with IC50 of 0.41 nM for Notch.

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Product Properties

• ALogP: 1.395
• hba_count: 4
• HBD Count: 3
• Rotatable Bond: 8

Names and Identifiers

• Isomeric SMILES: C[C@@H](C(=O)N[C@H]1C2=CC=CC=C2C3=C(N=CC=C3)N(C1=O)CCO)NC(=O)CCC(F)(F)F
• Molecular Weight: 464.44
• Reaxy-Rn: 54940485
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=54940485&ln=

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro
• DMSO(mg / mL) Max Solubility: 92
• DMSO(mM) Max Solubility: 198.08802
• Water(mg / mL) Max Solubility: ＜1