myxopyronin myxopyronin myxopyronins (myx) are a group of alpha-pyrone antibiotics, which are inhibitors of bacterial rna polymerase (rnap). they target switch 1 and switch 2 of the rnap "switch region". rifamycins and fidaxomicin also target rnap, but target different sites in rnap. myxopyronins do not have cross-resistance with any other drugs so myxopyronins may be useful to address the growing problem of drug resistance in tuberculosis. they also may be useful in treatment of methicillin-resistant staphylococcus aureus (mrsa). they are in pre-clinical development and has not yet started clinical trials. myxopyronin was first isolated in 1983 from a soil bacterium by werner kohl and herbert irschik at the helmholtz centre for infection research (former gbf). a total synthesis of myxopyronin was first reported in 1998 by james s. panek and co-workers. the target, the mechanism of action, and the structure of the complex of rnap with myxopyronin were first reported in 2008 by richard h. ebright and co-workers. synthetic analogs of the natural myxopyronins have been synthesized at anadys pharmaceuticals and at rutgers university. terence i. moy and co-workers at cubist pharmaceuticals have stated that, based on high resistance rate and high serum protein binding (comparable to rifamycins and lipiarmycin), the unmodified natural product myxopyronin b is not a viable starting point for antibiotic development. chemical structures of myxopyronin a (left) and myxopyronin b (right)