SY-589 is an orally active DNA polymerase Poltheta helicase domain inhibitor (IC50=2.29 nM) and DNA damage inducer. SY-589 inhibits the ATPase activity of the Poltheta helicase domain and blocks the Poltheta-mediated microhomology-mediated end joining (MMEJ) DNA repair pathway (IC50=0.85 nM). SY-589 also induces the accumulation of DNA double-strand breaks by increasing gamma-H2AX levels. SY-589 exerts antiproliferative effects on BRCA2-deficient cells and is used in the research of HR-deficient tumors[1].
