GN-1062 demonstrates clinical efficacy against uveal melanoma by inhibiting CDK7
Uveal melanoma (UM) is notable for being both the rarest form of melanoma and the most common type of eye cancer. Although some FDA-approved therapies exist, none have established themselves as the standard of care. Once UM metastasizes, treatment becomes particularly challenging, leading to a grim prognosis where half of the patients succumb within 10 years of diagnosis, underscoring a critical need for more effective treatments. The DepMap analysis has identified Cyclin-dependent kinase 7 (CDK7) as a crucial gene in UM. CDK7 is an enzyme involved in various cellular functions such as cell cycle progression, transcription, and cancer development. Dr. Sharma’s drug discovery lab has developed TGN-1062, a reversible inhibitor designed to block CDK7 and its downstream pathways that contribute to cancer persistence. ATP-detecting viability assays and western blotting were employed to evaluate the efficacy of TGN-1062 against UM cell lines. The results showed that TGN-1062 has an IC50 of approximately 1 μM across four tested cell lines. Additionally, western blot analysis indicated promising changes in the expression of CDK7-related biomarkers following treatment. These findings support the hypothesis that TGN-1062 disrupts UM cell health by inhibiting CDK7, demonstrating effective IC50 values in the low micromolar range and influencing relevant biomarkers.
