2,6-bis(pyridin-4-ylmethylene)cyclohexanone

RL91 (2,6-bis(pyridin-4-ylmethylene)cyclohexanone) is a synthetic cyclohexanone derivative that functions as a catalytic inhibitor of DNA topoisomerase I. Unlike topoisomerase I poisons such as camptothecin, which stabilize the covalent enzyme-DNA cleavable complex and lead to double-strand breaks, RL91 inhibits the catalytic activity of the enzyme itself. In preclinical studies, RL91 has demonstrated selective growth inhibition against tamoxifen-resistant breast cancer cell lines, including TamR3 and TamC3 sub-lines of MCF-7. The compound induces S-phase selective DNA damage, evidenced by the phosphorylation of histone H2AX. RL91 serves as a lead compound for the development of novel DNA-damaging agents specifically targeting cancers that have acquired resistance to endocrine therapies.

Other names

2,6-bis(pyridin-4-ylmethylene)cyclohexanone