SI-12

SI-12 is a small molecule inhibitor of the steroid receptor coactivator (SRC/p160) family, with high potency against steroid receptor coactivator 3 (SRC-3, also known as NCoA3 or AIB1). Developed by researchers at Baylor College of Medicine, SI-12 is a fluorinated analog of the earlier SRC inhibitor SI-2, optimized to provide improved metabolic stability, a prolonged plasma half-life, and reduced cardiotoxicity. Mechanistically, SI-12 physically interacts with the nuclear receptor interaction domain (NRID) of SRCs, promoting their degradation and disrupting the recruitment of secondary coactivators like p300/CBP to active transcriptional complexes. This leads to significant epigenetic changes and downregulates oncogenic transcription factors (such as ERα, AR, E2F1, and NF-κB). SI-12 has demonstrated potent anti-proliferative and anti-metastatic activity in preclinical models of breast cancer (including triple-negative and endocrine-resistant ESR1-fusion-driven breast cancers), prostate cancer, and mantle cell lymphoma.

Other names

SRC-3-IN-2SRC3-IN-2SRC 3-IN-2