T6I-29-1A

T6I-29-1A is a novel tetrahydro-6-isoquinoline (T6I) based selective estrogen receptor modulator (SERM) being investigated for the treatment of estrogen receptor-alpha positive (ERα+) breast cancer. It is specifically designed to address endocrine therapy resistance, including cases driven by constitutively active ESR1 mutations (such as Y537S and D538G) that are common in advanced and metastatic disease. Mechanistically, T6I-29-1A induces a transcriptional program similar to the selective estrogen receptor degrader (SERD) fulvestrant, despite having different effects on ERα cellular accumulation. A key feature of its mechanism is the induction of Small Ubiquitin-like Modifier-1 (SUMO1), a post-translational modification factor associated with improved prognosis in ERα+ breast cancer. T6I-29-1A is currently in preclinical development, with research supported by institutions including Loyola University Chicago and the University of Chicago.