Precious Metals

[gfp927z]

Acurx - ACX-362E


https://www.sciencedirect.com/science/article/pii/S0968089619306637?via%3Dihub


>>> One promising DCBG derivative, N7-Morphilino-ethyl-N2-DCBG (ACX-362E, 7-MorEDCBG) has recently been selected for development as the first anti-clostridial agent. The in vitro antibacterial activities of ACX-362E were as potent as 13e against several low G?+?C Gram(+) strains screened (unpublished data), and it displayed MIC50 and MIC90 values (2 and 4?µg/mL) close to vancomycin and metronidazole against 23 different C. difficile strains, including vancomycin and metronidazole-resistant strains (Table 5). Its specificity for the novel pol IIIC target endows ACX-362E with strong potential for bypassing the resistance that is emerging in C. difficile during the prolonged application of the other agents in current use.49 <<<

>>> ACX-362E inhibited both C. difficile pol IIIC and B. subtilis pol IIIC by the same mechanism (Fig. 13).50, 51 It strongly suggests that it may be possible to develop a single “broad spectrum” variant of ACX-362E that is active against multiple low G?+?C Gram(+) pathogens, including pathogens which are resistant to the existing, “conventional” antibiotics — for example, MRSA, VRE and emergent strains that are resistant to linezolid or daptomycin. <<<

>>> ACX-362E has many desirable anti-C. difficile properties. This agent is poorly absorbed from the GI tract and essentially nontoxic when given orally.49 In a hamster model of C. difficile colitis, oral ACX-362E was as effective as oral vancomycin, the current agent of choice for treating severe forms of the human disease. Treatment for 7?days with ACX-362E at 50?mg/kg twice daily reduced the recurrence rate to 40% and delayed death when the disease recurred, and when the same treatment regimen was continued for a total of 14?days, there was no recurrence observed during the remainder of the 34-day observation period.49 Given these promising results, ACX-362E, as noted above, has now entered human trials, becoming the first pol IIIC-specific agent to enter clinical investigation.52 <<<

>>> Since ACX-362E, its derivatives, and other structurally related pol IIIC inhibitors act through a heretofore clinically unexploited mechanism, there is a good reason to believe they will not share cross-resistance with any available class of antibiotics. Furthermore, as fully synthetic molecules unrelated to any known natural products and devoid of any history of use in the food supply, pol IIIC inhibitors may eventually be extremely useful agents to treat such high-priority pathogenic bacteria as MRSA, VRE, and multi-drug-resistant Streptococcus pneumoniae, as well as Gram(+) bacteria showing resistance to other commonly used drugs like linezolid and daptomycin. <<<