Avagacestat

Avagacestat (BMS-708163) is a potent inhibitor of γ-secretase, with IC50s of 0.27 nM and 0.30 nM for Aβ42 and Aβ40 inhibition; Avagacestat (BMS-708163) also inhibits NICD (Notch IntraCellular Domain) with IC50 of 0.84 nM and shows weak inhibition of CYP2C19, with IC50 of 20 μM. Avagacestat can be used for Alzheimer disease research.

Product Specifications

CAS Number

[1146699-66-2]

Product Name Alternative

BMS-708163

UNSPSC

12352005

Hazard Statement

H315, H319, H335

Target

Notch; γ-secretase

Type

Reference compound

Related Pathways

Neuronal Signaling; Stem Cell/Wnt

Applications

Cancer-programmed cell death

Field of Research

Cancer

Assay Protocol

https://www.medchemexpress.com/BMS-708163.html

Purity

99.92

Solubility

DMSO : ≥ 100 mg/mL

Smiles

O=S(N([C@@H](C(N)=O)CCC(F)(F)F)CC1=CC=C(C2=NOC=N2)C=C1F)(C3=CC=C(Cl)C=C3)=O

Molecular Formula

C20H17ClF4N4O4S

Molecular Weight

520.89

Precautions

H315, H319, H335

References & Citations

[1]Gillman KW, et al. Letter Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable γ-Secretase Inhibitor. Med Chem Lett, 2010, 1 (3), 120-124.|[2]Crump CJ, et al. BMS-708,163 targets presenilin and lacks notch-sparing activity. Biochemistry. 2012 Sep 18;51 (37) :7209-11.|[3]Xie M, et al. γ Secretase inhibitor BMS-708163 reverses resistance to EGFR inhibitor via the PI3K/Akt pathway in lung cancer. J Cell Biochem. 2015 Jun;116 (6) :1019-27.|[4]Borghys H, et al. A canine model to evaluate efficacy and safety of γ-secretase inhibitors and modulators. J Alzheimers Dis. 2012;28 (4) :809-22.|[5]Vladimir Coric, et al. Safety and tolerability of the γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol. 2012 Nov;69 (11) :1430-40.