MSK investigators have identified a novel and potent antimicrobial agent that demonstrates in vitro bactericidal activity against a wide range of drug-resistant gram-positive and gram-negative bacteria. SKI-356313, an imidazoline antimicrobial compound, also demonstrates proof-of-principle in vivo efficacy in models of pneumococcal and MRSA infection.
MSK investigators have utilized a combination of genetics, whole genome sequencing, and a novel target ID approach to show that SKI-356313 inhibits DNA replication and displaces the replisome from the bacterial nucleoid. These results identify a new antimicrobial scaffold with potential therapeutic utility against a number of growing global health threats.
- New antimicrobial scaffold
- Potential therapeutic utility against nonreplicating M. tuberculosis and antibiotic-resistant gram-positive cocci, including MRSA and VRE
- To date, no spontaneous drug-resistant mutants have been obtained, suggesting development of resistance will be minimal
Bacterial antimicrobial resistance is an escalating global health threat. Yet only two new systemic antibiotics have been approved by the U.S. FDA since 2009, and the current antimicrobial pipeline is severely depleted. SKI-356313 offers the potential to address an urgent health need.
PCT application published, PCT/US2013/069639; national applications pending in U.S., Canada, and Europe
Harris et al., ACS Chem Biol. 2014 Nov 21;9(11):2572-83.
Michael Glickman, MD, Laboratory Head, Immunology Program, Sloan Kettering Institute, MSK