Achaogen is pursuing an advanced series of LpxC inhibitor compounds that are active against Pseudomonas aeruginosa

LpxC can be an essential enzyme for the formation of the bacterial outer membrane and is highly conserved among gram-negative species. Development of Achaogen’s preclinical LpxC inhibitor compounds is supported by up to $5 million in funding from a contract with National Institute of Allergy and Infectious Diseases (NIAID). In July 2017, Achaogen was awarded a grant by Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X), an international antimicrobial consortium to accelerate global antibacterial innovation and research, to support the development of LpxC.

Inhibition of LpxC disrupts the structural integrity of the bacterial membrane, reducing its capacity to protect the cell from toxic molecules in the extracellular milieu and retain vital molecules in the space between the outer and inner membrane, leading to bacterial cell death.

Achaogen has improved on known LpxC inhibitors to generate a series of promising molecules that show improved safety in preclinical models, and better pharmaceutical properties. Given their novel mechanism of action, compounds generated in this program demonstrate no cross-resistance with current antibiotics and therefore retain activity against strains harboring resistance mechanisms that inactivate many other marketed antibiotics.

Review our literature on LpxC Inhibitors.