VKT-17-P4-23

VKT-17-P4-23 is a blood-brain barrier-permeable DksA inhibitor targeting the highly conserved transcriptional regulator DksA in Gram-negative bacteria, with a Kd value of 124 μM. Through modulation of the DksA-regulated SPI-2-dependent survival pathway, VKT-17-P4-23 exhibits antibacterial activity against planktonic and intracellular pathogens including Salmonella and additionally demonstrates activity against persistent bacterial populations that are difficult to eradicate. VKT-17-P4-23 is applicable to investigations involving Salmonella infection, bacterial persistence mechanisms, and transcriptional regulation in pathogenic bacteria.

DksA:124μM(Kd)

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

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, including measurable tissue distribution that crosses the blood-brain barrier, and displays an intravenous t1/2 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 histopathological lesions in the liver, and restores plasma liver enzyme levels to normal[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].