LCI132

LCI132 is a multitargeted small molecule inhibitor developed by the Molecular Targeted Therapeutics Laboratory at the Levine Cancer Institute (Atrium Health). It is part of a series of compounds designed to simultaneously inhibit multiple signaling pathways, specifically Phosphoinositide 3-kinase (PI3K), Bromodomain-containing protein 4 (BRD4), Cyclin-dependent kinase 4/6 (CDK4/6), and Cyclin-dependent kinase 9 (CDK9). The drug is intended to induce synthetic lethality in cancer cells, particularly in endometrial carcinoma, by targeting compensatory molecular signaling pathways within a single inhibitory domain. This approach aims to circumvent the toxicity and complex pharmacokinetics associated with combination therapies while preventing acquired resistance through kinome adaptation. Preclinical studies have shown that LCI132 decreases the gene expression of HEXIM1 and the anti-apoptotic protein MCL1 in endometrial carcinoma cell lines.