Nutshell Therapeutics Polθ inhibitor

Nutshell Therapeutics is developing a small-molecule inhibitor of DNA polymerase theta (Polθ) for the treatment of solid tumors. Polθ is a specialized DNA polymerase that plays a critical role in microhomology-mediated end joining (MMEJ), an alternative DNA double-strand break repair pathway. The therapeutic rationale relies on synthetic lethality, where Polθ inhibition is expected to selectively kill cancer cells that are deficient in homologous recombination (HR) repair, such as those harboring BRCA1 or BRCA2 mutations. By blocking the MMEJ pathway, which HR-deficient cells rely on for survival, the inhibitor induces genomic instability and cell death. The program is currently in the Lead to Preclinical Candidate (PCC) stage.

Other names

Polθ inhibitorDNA polymerase theta inhibitorPOLQ inhibitor