VKT-17-P4-23

VKT-17-P4-23 is a blood-brain barrier-permeable DksA inhibitor. DksA is a highly conserved transcriptional regulator in Gram-negative bacteria, with a K d of 124 μM. Through the DksA-regulated, SPI-2-dependent survival pathway, VKT-17-P4-23 exhibits antibacterial activity against both planktonic and intracellular pathogens such as Salmonella, and also effectively combats persistent bacteria that are difficult to eliminate. VKT-17-P4-23 can be used in studies of Salmonella infection ^[1].

In Vivo, VKT-17-P4-23 (1-10 mg/kg; i.v., i.p., p.o.; single dose) exhibits favorable pharmacokinetic properties in healthy male Sprague-Dawley rats, with measurable tissue distribution including passage across the blood-brain barrier, and an intravenous half-life of 2.68 hours^[1]. VKT-17-P4-23 (10 mg/kg; i.p.; every 12 hours; 12 hours pre-infection plus 3 total post-infection doses) significantly reduces Salmonella burden in systemic murine infection, eliminates liver histopathological lesions, and normalizes plasma liver enzyme levels^[1]. VKT-17-P4-23 (10 mg/kg; i.p.; every 12 hours; 12 hours pre-infection plus 3 total post-infection doses) significantly reduces Salmonella burden in both gastrointestinal and systemic tissues during oral murine salmonellosis^[1].

In Vitro, VKT-17-P4-23 (16 μg/mL; 20 h) inhibits growth of S. Typhimurium ATCC strain 14028s in EG minimal medium with an MIC of 16 μg/mL^[1]. VKT-17-P4-23 (≥4 μg/mL; 20 h) inhibits growth of intracellular S. Typhimurium in J774 macrophage-like cells in a dose-dependent manner, with significant activity at concentrations ≥4 μg/mL^[1]. VKT-17-P4-23 (16 μg/mL; 20 h) significantly reduces survival of in vitro-selected persistent S. Typhimurium cells exposed to DNA synthesis inhibitors^[1].

References:
[1]. Kim JS, et al. DksA inhibitors against intracellular and persistent Salmonella are effective in acute models of infection. Sci Adv. 2026 Mar 20;12(12):eaea6832.