Infectious disease

In vitro and mouse studies identified a hydroxamate-based LpxC inhibitor that could help treat Pseudomonas aeruginosa infections. Chemical synthesis and in vitro testing of hydroxamate analogs identified a compound that inhibited P. aeruginosa LpxC with an IC₅₀ of 1 nM. In cultures of 180 clinical isolates of P. aeruginosa, the compound inhibited growth with minimum inhibitory concentration (MIC) values of 60-400 nM/mL. In a mouse model of P. aeruginosa-induced pneumonia, IV delivery of the compound decreased bacterial burden in the lungs compared with vehicle. In a mouse model of P. aeruginosa infection of the thigh, subcutaneous delivery of the compound decreased bacterial burden in the thigh.Next steps by Novartis AG could include testing the safety and PK/PD of the compound in the infection models.

A2A Pharmaceuticals LLC has AA-001, an LpxC inhibitor, in preclinical testing to treat Gram-negative infection...