GKL003

GKL003 is a bacterial transcription inhibitor that targets the RNAP-σ interaction interface, with a K_i of 5.79 nM. GKL003 specifically binds to the RNAP β' clamp helix region at the σ^A factor binding site, blocks the formation of RNAP holoenzyme, and inhibits the formation of bacterial transcription initiation complexes. GKL003 inhibits the growth of both Gram-positive and Gram-negative bacterial cells, and also exhibits activity against drug-resistant strains^[1]. In Vitro:GKL003 (0.5-25 μM) inhibits in vitro transcription by the E. coli RNAP core enzyme combined with B. subtilis σᴬ, with stronger inhibitory activity observed at the subsaturating σᴬ:RNAP core enzyme ratio of 0.5:1^[1].
GKL003 (0-500 nM) inhibits the in vitro transcription activity of E. coli RNAP core enzyme with B. subtilis σᴬ, with an inhibition constant K_i of 5.79 nM^[1].
GKL003 (10-500 nM) inhibits the in vitro transcription activity of the E. coli RNAP core enzyme with E. coli σ^70[1]. In Vivo:GKL003 (1-2 mM) significantly inhibits the growth of Gram-negative E. coli DH5α cultures at concentrations ≥ 1 mM^[1].
GKL003 (0.5-2 mM) significantly inhibits the growth of Methicillin (HY-121544)-resistant Gram-positive Staphylococcus aureus strain USA300 at concentrations ≥ 1 mM, and dose-dependently suppresses transcription in viable S. aureus USA300 cells^[1].