Metallo-β-lactamase inhibitor

Project MDV

Metallo-β-lactamases confer high level resistance to the majority of β-lactam antibiotics, including last line of defence agents such as the carbapenems.

The AMR Centre is developing a metallo-β-lactamase inhibitor that restores the activity of β-lactams in Gram-negative microorganisms harbouring these resistance determinants, for the treatment of serious infections in combination with a carbapenem.

The AMR Centre signed an agreement acquiring worldwide rights to Medivir’s research stage Metallo-β-lactamase inhibitor (MBLI) program on 5 October 2017. This key research program is aimed at tackling the threat posed by NDM-1 and other metallo-β-lactamases, enzymes that make bacteria resistant to widely used beta-lactam antibiotics such as penicillin.

Target product

IV combination therapy for Gram-negative infections (MBL producing) with carbapenem

  • Septicaemia, pneumonia, urinary tract infections, intra-abdominal infection etc.
  • Carbapenem-resistant P. aeruginosa, A. baumannii and Enterobacteriaceae critical unmet medical need

Mechanism

Inhibition of Metallo-β-lactamases (MBL)

  • Provide resistance to all known classes of β-lactams (except monobactams)
  • Restore activity of last line of defence antibiotics – carbapenems
Data source: Public Health England
PDB: 3SPU · Ref: King & Strynadka (2011)