TBI-001

TBI-001 is a selective small molecule inhibitor of Tribbles homolog 2 (TRIB2), a pseudokinase that is highly upregulated in enzalutamide-resistant and neuroendocrine prostate cancer. TRIB2 acts as an oncogenic driver of lineage plasticity and therapeutic resistance. TBI-001 suppresses tumor growth and restores anti-tumor immunity by downregulating the expression of immune checkpoint molecules, specifically B7-H3 (CD276) and PD-L1 (CD274), on the surface of cancer cells. This reduction in checkpoint proteins enhances CD8+ T-cell activation and cytotoxicity, providing a dual therapeutic approach that targets both the tumor cells and the immunosuppressive microenvironment. It is currently being investigated for its potential to overcome enzalutamide resistance in advanced prostate cancer.