NU7774

NU7774 is a small molecule inhibitor of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Developed through research at institutions including Newcastle University and the Icahn School of Medicine at Mount Sinai, it is being explored as a therapeutic strategy to counter immune evasion in small cell lung cancer (SCLC) and other high-grade neuroendocrine tumors. NU7774 functions by reversing the repression of major histocompatibility complex class I (MHC-I) and antigen presentation (AP) machinery. Specifically, its inhibition of DNA-PKcs leads to the upregulation of HLA-A/B/C, TAP1, and TAP2, and triggers the STING (Stimulator of Interferon Genes) pathway, which increases CD8+ T-cell infiltration. In preclinical studies, NU7774 has demonstrated the ability to enhance the efficacy of immune checkpoint inhibitors, such as anti-PD-L1, leading to significant tumor regression in aggressive murine models of SCLC.