KSP-1007 is a potent, broad-spectrum boronic acid β-lactamase inhibitor, strongly inhibits class A carbapenemase KPCs with Ki app values of 0.836-2.19 nM, inhibits all β-lactamases from classes A, B, C, and D, enhances meropenem against carbapenem-resistant Gram-negative bacteria.
KSP-1007 is a potent inhibitor of class D carbapenemases, OXAs from Acinetobacter spp., and OXA-48 with Ki app of 0.621 to 5.78 nM.
KSP-1007 also inhibits class B metallo-β-lactamases (MBLs) with Ki app values ranging from 31.6 nM to 1.21 µM (except for IMP-6).
KSP-1007 also has activity against SHV-2, SHV-5, SHV-12, TEM-10, and ACT-17 were 361, 127, 53.5, 6.90, and 38.3 nM, respectively.
KSP-1007 (4 to 16 µg/mL) restored the activity of MEM, with MIC50 and MIC90 decreasing to ≤0.06 and 8 µg/mL for the combination of MEM/KSP-1007 (4 µg/mL), ≤0.06 and 1 µg/mL for the combination of MEM/KSP-1007 (8 µg/mL), and ≤0.06 and 0.25 µg/mL for the combination of MEM/KSP-1007 (16 µg/mL), respectively.
The in vitro activity of MEM/KSP-1007 at ≥4 µg/mL against Enterobacterales harboring metallo-β-lactamase was superior to that of cefepime/taniborbactam.
MEM/KSP-1007 showed excellent activity against Escherichia coli with PBP3 mutations and New Delhi metallo-β-lactamase compared to aztreonam/avibactam, cefepime/taniborbactam, and cefiderocol.
KSP-1007 enhanced the in vivo activity of MEM against carbapenemase-producing Enterobacterales, A. baumannii, and P. aeruginosa in murine systemic, complicated urinary tract, and thigh infection models.