IBCar Potent Orally Bioavailable Methyl N-[5-(3'- iodobenzoyl)-1H-benzimidazol-2-yl]carbamate for Breast Cancer Therapy

This study examined the efficacy and mechanisms underlying biological activities of IBCar in several in vitro and in vivo breast cancer models and in cells derived from normal tissues. The IBCar’s effectiveness was demonstrated across a diverse range of BCa cell lines, including those with mutant and wild-type TP53 as well as cell lines with short and long doubling times. Comparative analysis of IBCar’s effects on normal versus cancer cells revealed distinct responses, including differences in endoplasmic reticulum stress, mitochondrial membrane potential, and cell death pathways. IBCar is cytotoxic to breast cancer cells at nM concentrations and induces apoptosis. In normal cells, the key protective mechanisms in response to IBCar appear to involve reversible microtubule depolymerization and pro-survival adaptations within the caspase-8 and ripoptosome pathways. IBCar-induced irreversible microtubule depolymerization, leading to mitochondrial dysfunction and endoplasmic reticulum stress, was observed in cancer cells but not in normal cells, highlighting its selective cytotoxicity. The therapeutic efficacy of IBCar was further validated in mouse models of triple-negative and Luminal B breast cancers. In both models, IBCar exhibited strong antitumor activity without inducing observable toxicity. Overall, these findings support the potential of IBCar as an effective and non-toxic alternative for breast cancer treatment.