SP-1-303

SP-1-303 is a novel, second-generation small molecule that acts as a dual-targeting class I histone deacetylase (HDAC) inhibitor and ataxia-telangiectasia mutated protein (ATM) activator. It selectively inhibits HDAC1 and HDAC3, with additional activity against HDAC6, and demonstrates potent growth inhibition of estrogen receptor positive (ER+) breast cancer cells at low micromolar concentrations. Mechanistically, SP-1-303 decreases ER-alpha expression, increases p53 expression, induces phosphorylation of ATM and its substrates BRCA1 and p53, and increases PD-L1 expression in a time-dependent manner. These properties suggest potential for combination therapy with immune checkpoint inhibitors. The compound shows significantly lower toxicity to normal breast epithelial cells compared to cancer cells. Pharmacokinetic studies in rats indicate an intravenous elimination half-life of approximately 1.26 hours. Developed by Shuttle Pharmaceuticals Holdings as part of their preclinical pipeline focused on radiation sensitization and targeted cancer therapy[1][2][3][4][5][7].