LMP135

LMP135 is a novel fluoroindenoisoquinoline derivative and a non-camptothecin topoisomerase I (TOP1) inhibitor developed as an anticancer agent. Unlike camptothecin analogues such as topotecan, LMP135 retains potent TOP1 cleavage complex (TOP1cc) trapping and antiproliferative activity, owing to a single 3-fluoro substituent designed to improve metabolic stability. LMP135 shows robust antitumor activity in preclinical small cell lung cancer (SCLC) xenograft models, with better potency than topotecan and other parent indenoisoquinolines. The cellular response to LMP135 is highly dependent on the expression of Schlafen 11 (SLFN11), a gene associated with the efficacy of DNA-damaging agents. LMP135 causes DNA damage marked by γH2AX and demonstrates higher activity in SLFN11-proficient cells. It is being developed primarily for cancer indications, notably SCLC, but has potential broad anticancer utility as a TOP1 inhibitor[1][3].