BMS-708,163 targets presenilin and lacks notch-sparing activity.

  title={BMS-708,163 targets presenilin and lacks notch-sparing activity.},
  author={Christina J Crump and Suita V Castro and Feng Wang and Nikolay Pozdnyakov and T Eric Ballard and Sangram S. Sisodia and Kelly R. Bales and Douglas Scott Johnson and Yue-Ming Li},
  volume={51 37},
The "Notch-sparing" γ-secretase inhibitor (GSI) BMS-708,163 (Avagacestat) is currently in phase II clinical trials for Alzheimer's disease. Unlike previously failed GSIs, BMS-708,163 is considered to be a promising drug candidate because of its reported Notch-sparing activity for the inhibition of Aβ production over Notch cleavage. We now report that BMS-708,163 binds directly to the presenilin-1 N-terminal fragment and that binding can be challenged by other pan-GSIs, but not by γ-secretase… CONTINUE READING