Novel inhibitors of PARP1 and PARP14: design, synthesis, and potentiation of cisplatin efficacy in cancer.

ABSTRACT:

Background

Poly(ADP-ribose) polymerase (PARP) is a superfamily of enzymes involved in cell survival. Both PARP1 and PARP14 are overexpressed in malignancies. No clinically approved PARP14 inhibitors are available, and PARP1 inhibitors are generally nonspecific, resulting in a need for a more diverse library of selective PARP1 and PARP14 inhibitors.

Materials and methods

Based on the previous lead compounds 1 and 2, 26 novel compounds were designed, synthesized, and screened against PARP1 and PARP14. Compounds with the best in vitro inhibitory results were further screened against PARP2, PARP3, PARP5a, PARP7, and PARP15.

Results and conclusion

The 26 novel compounds demonstrated a lesser inhibitory effect than the lead compounds. Compounds 1 and

SUBMITTER: Kam CMT 

PROVIDER: S-EPMC11703142 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature