Myxopyronin (Myx) is an alpha-pyrone antibiotic, the first in a new class of inhibitors of bacterial RNA polymerase (RNAP) that target switch 1 and switch 2 of the RNAP "switch region." Rifamycin antibacterial agents, which are first-line treatments for tuberculosis, and lipiarmycin (fidaxomicin, Dificid) also target RNAP, but target different sites in RNAP. Myxopyronin does not have cross-resistance with rifamycins and lipiarmycin. Myxopyronin may be useful to address the growing problem of drug resistance in tuberculosis. It also may be useful in treatment of methicillin-resistant Staphylococcus aureus (MRSA). It is in pre-clinical development and has not yet started clinical trials.
Myxopyronin was first isolated in 1983 from a soil bacterium by Rolf Jansen and Herbert Irschik. 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. Novel analogs of myxopyronin have been synthesized at Anadys Pharmaceuticals (San Diego, CA) and at Rutgers University (Piscataway, NJ). Terence I. Moy and co-workers at Cubist Pharmaceuticals (Lexington, MA) 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.
- Irschik, Herbert (1983), Journal of Antibiotics http://www.journalarchive.jst.go.jp/jnlpdf.php?cdjournal=antibiotics1968&cdvol=36&noissue=12&startpage=1651&lang=en&from=jnlabstract
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- Srivastava A, Talaue M, Liu S, Degen D, Ebright RY, Sineva E, Chakraborty A, Druzhinin SY, Chatterjee S, Mukhopadhyay J, Ebright YW, Zozula A, Shen J, Sengupta S, Niedfeldt RR, Xin C, Kaneko T, Irschik H, Jansen R, Donadio S, Connell N, Ebright RH (August 2011), "New target for inhibition of bacterial RNA polymerase: 'switch region'", Curr Opin Microbiol, doi:10.1016/j.mib.2011.07.030, PMC 3196380, PMID 21862392
- Terence I. Moy, Anu Daniel, Crystal Hardy, Andrew Jackson, Owen Rehrauer, You Seok Hwang, Dong Zou, Kien Nguyen, Jared A. Silverman,Qingyi Li, Christopher Murphy (2011), "Evaluating the activity of the RNA polymerase inhibitor myxopyronin B against Staphylococcus aureus", FEMS Microbiology Letters 319 (2): 176–179, doi:10.1111/j.1574-6968.2011.02282.x
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