ribocil

Description: Ribocil is a novel, potenty and highly selective chemical modulator of bacterial riboflavin riboswitches. Ribocil strongly inhibits GFP expression, achieving a 50% effective concentration (EC50) of 0.3 uM. Ribocil is a highly specific bioactive synthetic mimic of FMN, which competes with the natural ligand to inhibit FMN riboswitch-mediated expression of ribB and inhibits bacterial growth. Ribocil-B demonstrates superior microbiological activity as compared to Ribocil-A (minimum inhibitory concentration (MIC) = 1 ug/ml versus MIC >= 64 ug/ml), inhibition of riboflavin synthesis (IC50 = 0.13 uM versus IC50 > 26 uM), and binding affinity to the E. coli FMN aptamer (Kd = 6.6 nM versus Kd >= 10, 000 nM). Riboswitches are non-coding RNA structures located in messenger RNAs that bind endogenous ligands, such as a specific metabolite or ion, to regulate gene expression. As such, riboswitches serve as a novel, yet largely unexploited, class of emerging drug targets. Demonstrating this potential, however, has proven difficult and is restricted to structurally similar antimetabolites and semi-synthetic analogues of their cognate ligand, thus greatly restricting the chemical space and selectivity sought for such inhibitors.

References: Nature. 2015 Oct 29; 526(7575):672-7.