 | This article needs to be updated.(September 2020) |
Myxopyronins (Myx) are a group of alpha-pyrone antibiotics, which are inhibitors of bacterial RNA polymerase (RNAP). [1] [2] They target switch 1 and switch 2 of the RNAP "switch region". [3] 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. [4] 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). [1] A total synthesis of myxopyronin was first reported in 1998 by James S. Panek and co-workers. [5]
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. [6] [7] Synthetic analogs of the natural myxopyronins have been synthesized at Anadys Pharmaceuticals and at Rutgers University. [8] [9]
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. [10]
