Description:
Summary
Researchers at Oregon Health & Science University have discovered a class of compounds that are biologically active through a novel homologous recombination repair of DNA double-strand breaks mechanism of action. The lead compound is not cytotoxic, has proven activity in vivo, and represents a tremendous opportunity to develop the first selective drug for treatment for a variety of cancer types.
Technology Overview
DNA double-strand damages can be repaired by either homologous recombination (HR) or non-homologous end joining (NHEJ). Lamin A promotes genetic stability by maintaining the levels of proteins that have key roles in HR and NHEJ. Lamin A is an intermediate filament protein that enables rad51 to interact with strands of DNA and thus the observed biological activity in select cell types.
Compounds in this class inhibit the growth of multiple triple negative breast and ovarian cancer cell lines. In vitro GI50’s for select compounds are low double digit nanomolar. Note, data for best in class compounds are not shown in the data table.
Publications
Xiao, X. et al. Anticancer Pyrroloquinazoline LBL1 Targets Nuclear Lamins, ACS Chem Biol, 2018; 13:1380-1387.
Xiao, X. et al. Design, synthesis and evaluation of antitumor acylated monoaminopyrroloquinazolines, Bioorg Med chem Lett, 2017; 27:3107-3110.