SIM0508 + olaparib

SIM0508 + olaparib is an investigational combination therapy consisting of SIM0508, a potent and selective small molecule inhibitor of DNA polymerase theta (Pol θ), and olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor. This combination targets the DNA damage repair pathways in cancer cells with homologous recombination deficiency (HRD). Pol θ is essential for microhomology-mediated end joining (MMEJ), an alternative DNA repair pathway that HRD tumor cells rely on. By inhibiting both Pol θ and PARP enzymes, this combination aims to induce synthetic lethality in HRD tumors by blocking their primary and backup DNA repair mechanisms. Preclinical studies have shown favorable oral pharmacokinetics and safety for SIM0508 with low risk of additive toxicity when combined with PARP inhibitors like olaparib. The combination is being developed primarily for the treatment of locally advanced or metastatic solid tumors[2][4][7].

Other names

AZD2281AZD-2281AZD 2281KU-0059436KU0059436KU 0059436KU59436KU-59436KU 59436