KL-50

KL-50 is a novel imidazotetrazine-based small molecule designed as a precision chemotherapy agent for the treatment of glioblastoma, particularly in tumors that are deficient in O6-methylguanine-DNA methyltransferase (MGMT). Unlike temozolomide, which loses efficacy in MGMT-deficient or DNA mismatch repair (MMR)-deficient tumors, KL-50 induces DNA interstrand cross-links and subsequent double-stranded breaks independently of MMR status. Its mechanism involves alkylation at the O6 position of guanine to form O6-(2-fluoroethyl)guanine, leading to cross-linking and tumor cell death. Preclinical studies have shown that KL-50 selectively kills MGMT-deficient glioblastoma cells while sparing normal cells and is effective against both newly diagnosed and temozolomide-resistant GBM models. The drug has demonstrated oral bioavailability, CNS penetration, and favorable tolerability profiles in animal models. Modifi Bio is developing KL-50 for clinical use[1][2][3][4][5][7][8].

Other names

N3-(2-fluoroethyl)imidazotetrazine