Definition

An orally bioavailable inhibitor of DNA polymerase (pol) theta, with potential chemosensitizing and antineoplastic activities. Upon oral administration, pol theta inhibitor GSK4524101 specifically targets, binds to and inhibits the activity of pol theta. This prevents pol theta-mediated repair of double-stranded DNA breaks via the microhomology-mediated end joining (MMEJ) process. This causes apoptosis and inhibits proliferation in cancer cells. GSK4524101may have a synergistic effect if administered in combination with agents that cause DNA damage. Pol theta plays a key role in DNA synthesis and repair that is highly expressed in cancer cells while nearly absent in most healthy tissues. It plays a key role in cancer cell survival.