| Stereochemistry | ABSOLUTE |
| Molecular Formula | C20H17ClF4N4O4S |
| Molecular Weight | 520.885 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NC(=O)[C@@H](CCC(F)(F)F)N(CC1=CC=C(C=C1F)C2=NOC=N2)S(=O)(=O)C3=CC=C(Cl)C=C3
InChI
InChIKey=XEAOPVUAMONVLA-QGZVFWFLSA-N
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
Avagacestat (BMS-708163) is an oral gamma secretase inhibitor designed for selective inhibition of amyloid beta (Aβ) synthesis. Avagacestat was in development by Bristol-Myers Squibb for the treatment of Alzheimer's disease (AD). Avagacestat 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. In November 2012, Bristol-Myers Squibb terminated clinical trials of the drug and announced its decision to end further development of avagacestat
CNS Activity
Originator
Approval Year
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
PubMed
Sample Use Guides
Of the four Avagacestat (BMS-708163) doses evaluated (25 mg, 50 mg, 100 mg and 125 mg/day), doses below 100 mg/day demonstrated acceptable tolerability profiles for further development and were associated with discontinuation rates comparable with placebo. BMS-708163 doses at or above 100 mg were associated with higher discontinuation rates, most commonly due to gastrointestinal and dermatological side effects.
Route of Administration:
Oral
ACTIVE MOIETY
