SSTN-302

SSTN-302 is an orally bioavailable small-molecule inhibitor of the Notch1 transcriptional ternary complex being developed by StemSynergy Therapeutics for the treatment of Notch-driven cancers, including upper gastrointestinal malignancies. By specifically disrupting Notch1-mediated Notch transcriptional complex (NTC) formation at CSL-DNA, SSTN-302 selectively blocks Notch1-dependent transcriptional activation of oncogenic target genes, inhibiting proliferation and survival of Notch1-addicted tumor cells while sparing other Notch isoforms and minimizing the gastrointestinal toxicity typical of pan-Notch or gamma-secretase inhibitors.[4][5] Preclinical studies show potent inhibition of Notch signaling, regression of xenograft tumors, favorable ADME and high oral bioavailability, and the compound is undergoing IND-enabling safety studies with plans to advance into first-in-human trials in patients with advanced upper GI cancers.[1][4][5][9][11][13]