NADI-351 is a specific small-molecule inhibitor of Notch1 transcriptional complexes with IC50 of 8.8 uM in cellualr reporter assays.
NADI-351 inhibited OE33 cell growth in single dose MTT assays (EC50= 10 uM) and, more potently, in multi-dose colony formation assays (EC50=1.3 uM)
NADI-351 is 15 times more potent than IMR-1 in an NTC AlphaScreen assay.
NADI-351 selectively disrupted Notch1 transcription complexes, inhibited recruitment of Notch1 to the NTC (Notch Ternary Complex) and to the HES1 promoter, and reduced Notch1 recruitment to target genes.
NADI-351 inhibits tumor growth in Notch-dependent cancers and does not exert gastrointestinal toxicity associated with goblet cell metaplasia.
NADI-351 selectively inhibits stem-like esophageal adenocarcinoma (EAC) cell populations.
