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Platencin and platensimycin

Platencin and platensimycin are members of an exciting new class of antibiotics active against Gram positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).  Platensimycin inhibits FabF, a bacterial enzyme required for the synthesis of fatty acids and thus inhibition of the formation of the bacterial cell membrane (Wang J. et al. Nature 2006; 441: 358 - 361).  It is more potent and has a wider spectrum of activity than linezolid, a novel synthetic oxazolidinone, used clinically to treat various Gram positive antibiotic resistant infections.  Platencin appears to have a broader mode of action, inhibiting both FabF and FabH sites.  

BioAustralis is the first commercial supplier of this product and its analogue, platencin, for in vitro laboratory research purposes. 

 Liver X receptor antagonists

In 2002, Tangirala and co-workers identified Liver X receptors as targets for intervention in cardiovasular disease.  LXR alpha and LXR beta control transcription of genes critical to a range of biological functions, including regulation of high density lipoprotein cholesterol metabolism, hepatic cholesterol catabolism, and intestinal sterol absorption (Tangirala R.K. et al. Proc Natl Acad Sci U.S.A. 2002; 99(18): 11896-901).  In 2005, researchers from Merck isolated two new hexacyclic aromatic ketones, (-)-anthrabenzoxocinone and (-)-bischloroanthrabenzoxocinone ((-)-BABX), which exhibited binding to LXR alpha and inhibited Type II fatty acid synthesis (Kodali S. et al. JBC 2005; 280(2): 1669 - 1677, Herath R.K. et al. 2005; 68: 1437 - 1440).  BioAustralis is the first commercial supplier of BABX for in vitro laboratory research purposes.

Inhibitors of Heat Shock Protein 90

Hsp90 inhibitors are exciting intense interest as potential therapies in cancer, inflammatory diseases and neurodegenerative conditions – exemplified by Pfizer’s acquisition of Serenex Inc. in 2008.

Recently it was reported that the Hsp90 inhibitor, geldanamycin, has weak cytotoxic activity as a single agent, but it dramatically intensifies the cytotoxicity of doxorubicin and ICRF-193 in Jurkat and HL-60 cells.  These results suggest that abrogation of G2 checkpoint by geldanamycin may play a central role in sensitizing p53-negative tumor cells to DNA-damaging and decatenation-inhibiting agents (Sugimoto K. et al. Oncogene 2008; 27,:3091–3101).  Geldanamycin is also reported to augment the cytopathic effect of the measles virus in MDA-MB-231 (breast), SKOV3.IP (ovarian) and TE671 (rhabdomyosarcoma) cancer cell lines (Liu C. et al. Gene Therapy 2008; 15: 1024-1034).   

Hsp90 inhibitors:

 

 Other ansamacrolides sold by BioAustralis

 
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