Gut Toxicity of g-Secretase Inhibitors by Modulation of Notch Processing:Pathology and Gene Profiling.It is anticipated that g-secretase inhibitors (g-Sec-I) which modulate Notch processing will alter differentiation in tissues whose architecture is governed by Notch signalling.To explore this hypothesis,Han Wistar rats were dosed for up to 5 days with 10-100 mmol/kg bid g-Sec-I from 3 chemical series that inhibit Notch processing in vitro atvarious potencies (Notch IC50).These included an arylsulfonamide (AS) (142 nM),a dibenzazepine (DBZ)(1.7 nM),and a benzodiazepine (BZ)(2.2 nM).DBZ and BZ caused dose-dependent intestinal goblet cell metaplasia.