L024

L024 is a first-in-class, brain-permeant small molecule agent designed for the prevention and interception of estrogen receptor-negative (ER-neg) breast cancer, including triple-negative breast cancer (TNBC) and its associated brain metastases. Mechanistically, L024 inhibits SREBP1-driven lipogenesis, suppresses the PI3K-AKT signaling axis (specifically reducing pAKT at Ser473), and downregulates NF-κB-mediated inflammation. These pathways are critical for the progression and metastatic spread of ER-neg breast cancer. Developed by researchers at Northwestern University, L024 has demonstrated the ability to inhibit tumor growth, impair the invasion and migration of brain-tropic cells, and cross the blood-brain barrier with high brain exposure (Kp > 1). Its favorable pharmacokinetic profile and metabolic reprogramming capabilities make it a promising candidate for reducing the risk of brain dissemination in high-risk breast cancer populations.