Avagacestat (BMS-708163) 1146699-66-2

.cp_wz table {border-top: 1px solid #ccc;border-left:1px solid #ccc; } .cp_wz table td{border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc;border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;}


Molecular Weight:

520.88 Avagacestat (BMS-708163) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. Phase 2.






Biological Activity


BMS-708163 exhibits weaker selectivity for inhibition of Notch processing with 193-fold IC50 value.


Oral administration of BMS-708163 significantly reduces Aβ40 levels for
sustained periods in brain, plasma, and cerebrospinal fluid in rats and
dogs. BMS-708163 has no dose-limiting effects in dogs (3 mg/kg during 6
months), with a high brain to plasma ratio (2.4).






Inhibition of Aβ formation


BMS-708163 is assayed for Aβ40 or Aβ42 inhibition in cells using H4
APP751 SWE clone 8.20, an H4 neuroglioma cell line stably expressing the
Swedish mutant of APP751. Cells are maintained in log phase through
twice weekly passage at a 1:20 dilution. For IC50 determinations, 30 μL
cells (1.5×104 cells/well) in DMEM media containing 0.0125%
BSA are seeded directly into 384-well plates containing 0.1 μL serially
diluted BMS-708163 in DMSO.


Following incubation for 19 hours in 5% CO2 at 37 °C, plates are briefly centrifuged (103 rpm, 5 min). A 10 μL aliquot from each well is transferred to a second
assay plate for Aβ40 measurements. Antibody cocktails are freshly
prepared by dilution into 40 mM Tris-HCl (pH 7.4) with 0.2% BSA and
added to assay plates. For Aβ42 measurements, antibodies specific for
the Aβ42 neoepitope (565, developed at Bristol-Myers Squibb; conjugated
to the Wallac reagent) and the N-terminal sequence of Aβ peptide (26D6,
developed at SIBIA/Bristol-Myers Squibb; conjugated to APC) are mixed
and 20 μL of the mixture is added to each well of the incubated cell
plate yielding a final concentration of 0.8 ng/well 565 and 75 ng/well
26D6.


For the Aβ40 measurements, antibodies specific for the Aβ40
neoepitope (TSD, developed at Bristol-Myers Squibb; conjugated to the
Wallac reagent) and 26D6 as described above are mixed and 20 μL of the
mixture is added to the 10 μL aliquots which have been removed
previously from the cell plate yielding a final concentration of 1.6
ng/well TSD and 17.5 ng/well 26D6. Assay plates containing antibodies
are sealed with aluminum foil and incubated overnight at 4 °C. Signal is
determined using a Viewlux counter and IC50 values are determined.

Contact us if you need more details on 1146699-66-2. We are ready to answer your questions on packaging, logistics, certification or any other aspects about Avagacestat 1146699-66-2、BMS-708163 1146699-66-2. If these products fail to match your need, please contact us and we would like to provide relevant information.

Product Categories : Proteases > Gamma-secretase Inhibitor