A modern antibacterial target should meet the following criteria:
- Essential for bacterial life
- Entirely absent in humans
- Commonly found in a wide spectrum of bacteria
- A completely new antibiotic strategy
All antibiotics on the market today meet only the first three criteria. DeNovaMed's compounds satisfy all four. The fourth criterion is especially important to combat pathogens that have been in the patient population for a long time and have become used to coping with the usual suspects (penicillins, cephalosporins, tetracyclines, etc.). Methicillin-Resistant Staph. Aureus, Vancomycin Resistant Enterococcus, and FluoroQuinolone-Resistant Pseudomonas are on the rise such that they represent a significant fraction of all infections today. Until recently, if an infection proved resistant to a front-line drug, an alternative was effective; but this is no longer the case. The incidence of drug-resistant infections is reaching crisis levels in many hospitals, in part because antibiotic resistant organisms frequently lurk in the hospital setting. In the USA the number of cases exceeded 200,000 with more than 80,000 deaths.
Lipid metabolism targets in bacterial control the synthesis of a wide variety of essential bacterial components, including virulence factors, membrane structures, and fatty acids required for bacterial life. DeNovaMed’s lead program focuses on ACP synthase (AcpS), an upstream target that is present in Gram-positive, Gram-negative, and mycobacterium as well as in the Plasmodium malarial parasite. AcpS inhibitors therefore constitute an important broad-spectrum strategy for antibiotics .