Nirogacestat exhibits strong antitumor effects in a 14-day study involving twice-daily dosing with tumor growth suppression being dose-dependent. The greatest reduction in tumor growth, approximately 92%, is seen at higher doses (150 mg/kg). Continuous dosing at less than 100 mg/kg is generally well tolerated in mice for over a week, showing no significant weight loss, morbidity, or mortality. However, an increase to 150 mg/kg leads to symptoms such as diarrhea and weight loss of 10-15% around ten days post-administration. A return to normal body weight is often observed after pausing the treatment, indicating the reversible nature of Nirogacestat's toxicity^[1].

In cell-free assays measuring Aβ production from HeLa cell-derived membranes, Nirogacestat achieves a γ-secretase inhibition IC50 of 6.2 nM. Cellular assays using HPB-ALL cells, which possess mutations in both the heterodimerization and PEST domains of Notch1, reveal an IC50 of 13.3 nM for inhibiting Notch receptor cleavage. Moreover, a 7-day treatment with Nirogacestat results in a notable elevation in caspase-3 activity and the appearance of cleaved PARP and caspase-3 in HPB-ALL and TALL-1 cells^[1].