BMS-708163 (Avagacestat) --- γ-Secretase Inhibitor

BMS-708163 (Avagacestat) is a potent, selective and orally bioavailable γ-secretase inhibitor with an IC50 of 0.3 nM for APP cleavage. It is 190-fold more selective for APP than Notch, having an IC50 of 58 nM for Notch. Phase I clinical trial studies showed that in humans, BMS-708163 decreased CSF Aβ40 and Aβ42 approximately 30% following daily dose of 100 mg after 28 days and by 60% at daily dose of 150 mg.

Product information

CAS Number: 1146699-66-2

Molecular Weight: 520.88

Formula: C20H17ClF4N4O4S

Synonym:

Avagacestat

Chemical Name: (R)-2-(4-chloro-N-(2-fluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide

Smiles: NC(=O)[C@@H](CCC(F)(F)F)N(CC1=CC=C(C=C1F)C1=NOC=N1)S(=O)(=O)C1C=CC(Cl)=CC=1

InChiKey: XEAOPVUAMONVLA-QGZVFWFLSA-N

InChi: InChI=1S/C20H17ClF4N4O4S/c21-14-3-5-15(6-4-14)34(31,32)29(17(18(26)30)7-8-20(23,24)25)10-13-2-1-12(9-16(13)22)19-27-11-33-28-19/h1-6,9,11,17H,7-8,10H2,(H2,26,30)/t17-/m1/s1

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

BMS-708163 was used at 1-10 µM in vitro.

In Vivo:

BMS-708163 was dosed orally in female rats at 10 and 100 mg/kg once per day, and could significantly reduced both plasma and brain Aβ40 levels relative to control for the entire dosing interval.

References:

1. BMS-708163 was dosed orally in female rats at 10 and 100 mg/kg once per day, and could significantly reduced both plasma and brain Aβ40 levels relative to control for the entire dosing interval.
2. Mitani Y, et al. Differential effects between γ-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. (2012) J Neurosci. 32(6):2037-50.

Products are for research use only. Not for human use.

Documents