LX-1S

LX-1S 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 as an analog of LX-1, LX-1S is being investigated for the treatment of advanced, antiandrogen-resistant prostate cancer. The compound works by simultaneously inhibiting AR signaling and the AKR1C3-mediated synthesis of intratumoral androgens, which are key drivers of resistance to standard therapies like enzalutamide and abiraterone. Preclinical studies have demonstrated that LX-1S possesses superior bioavailability and efficacy compared to its predecessor, showing significant reduction in tumor growth and intratumoral testosterone levels in xenograft and patient-derived xenograft (PDX) models. Furthermore, LX compounds have shown potential to synergize with standard-of-care treatments such as enzalutamide, abiraterone, and docetaxel.