LX-1

LX-1 is a novel small molecule dual inhibitor designed to target both the androgen receptor (AR), including its splice variants such as AR-V7, and the enzyme aldo-keto reductase family 1 member C3 (AKR1C3). Developed by researchers at the University of California, Davis and The Ohio State University, LX-1 aims to overcome resistance to standard antiandrogen therapies in advanced prostate cancer. AKR1C3 plays a critical role in intratumoral androgen synthesis, while AR-V7 is a common driver of resistance to drugs like enzalutamide and abiraterone. Preclinical studies have demonstrated that LX-1 effectively binds to the AKR1C3 active site, reduces AR/AR-V7 expression, and inhibits tumor growth in xenograft and patient-derived xenograft (PDX) models. It has also shown synergistic potential when combined with standard therapies such as enzalutamide, abiraterone, and docetaxel.