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We have developed lead BPL antagonist BPL199, which is active against Staphylococcus aureus BPL and Mycobacterium tuberculosis with > 44m-fold less selectivity for human BPL.
About
BACKGROUND For more than half a century we have relied on a limited number of antibiotics to combat infections. However, the emergence of bacteria that are resistant to chemotherapy is rendering our current arsenal of antibiotics less effective and in some cases totally ineffectual. One well-accepted approach to address drug resistance is to develop new antibiotic classes that work through novel modes of action and that are not subject to existing resistance mechanisms. Chemotherapeutics that target biotin protein ligase (BPL) represent a novel class of antibiotic. TECHNOLOGY OVERVIEW We have successfully developed lead BPL antagonist BPL199, which is active against Staphylococcus aureus BPL and Mycobacterium tuberculosis with > 44 million-fold less selectivity for human BPL. - S.aureus BPL Ki = 0.72 nM - M. tuberculosis BPL Ki = 0.74 nM - Human BPL Ki > 33 mM - Bacteriostatic activity against S. aureus is comparable to other antibiotics (MIC = 0.25 μg/ml).
Key Benefits
- Demonstrated mechanism of action through inhibition of BPL - Low rates of resistance (<1 x 10^9) - No cytotoxicity against two cell lines at 100x MIC - Tolerated in mice and rats (26 mg/kg).