SMT026738

**SMT026738 (SMT-738)** is a novel, first-in-class small-molecule antibiotic developed by Summit Therapeutics using its Discuva Platform. It targets the bacterial lipoprotein transport complex **LolCDE**, an essential and clinically unexploited target in Gram-negative bacteria, disrupting outer membrane integrity and leading to rapid bactericidal activity (within 2-4 hours). SMT026738 exhibits potent activity against **Enterobacterales**, including multi-drug-resistant *Escherichia coli* (MIC₉₀ 1 µg/mL) and *Klebsiella pneumoniae* (MIC₉₀ 2 µg/mL), as well as carbapenem-resistant Enterobacteriaceae (CRE), with low resistance potential (<10⁻⁹) and microbiome-sparing properties (inactive against Gram-positive and anaerobic gut commensals). It shows favorable **in vitro** safety (cytotoxicity IC₅₀ >200 µM in mammalian cells), good PK with high lung/kidney penetration and urinary excretion (~30% unchanged), and robust efficacy in murine models of bloodstream, pneumonia, and urinary tract infections. Supported by CARB-X funding, it addresses urgent CDC/WHO threats with no pre-existing resistance.[1][2][3][5][7][9]

Other names

DDS-04 seriesDDS04 seriesDDS 04 series