Biological Activity
PK150, an analogue of Sorafenib, shows oral bioavailability and antibacterial activity against several pathogenic strains at submicromolar concentrations. PK150 inhibits Gram-positive Methicillin-sensitive S. aureus (MSSA), Methicillin-resistant S. aureus (MRSA), Vancomycin intermediate S. aureus (VISA) with MICs of 0.3, 0.3-1, 0.3 µM, respectively[1].
In Vitro
No in vitro data are provided in the current product source. Contact us for further information.
In Vivo
The in vivo efficacy of PK150 against methicillin-sensitive S. aureus (MSSA) (strain SH1000) is demonstrated in a murine bloodstream infection model. PK150 (20 mg/kg; p.o.) significantly reduces bacterial loads in the liver and heart[1]. PK150 (10 and 20mg/kg orally; or 10mg/kg intravenously) shows no obvious signs of toxicity in mice. Higher i.v. dosing of 20mg/kg results in severe toxic effects and is thus avoided for subsequent therapeutic models[1]. Animal Model: Pathogen-free 9-week old female C57BL/6J mice[1] Dosage: 20 mg/kg Administration: Administered p.o. Result: Bacterial loads in the liver and heart were both significantly reduced by approximately 100-fold. Animal Model: Outbred male CD-1 mice, 4 weeks old[1] Dosage: 10 and 20 mg/kg (Pharmacokinetic Analysis) Administration: Administered by intragastric gavage at 10 and 20 mg/kg or intravenously at 10 mg/kg Result: Oral bioavailability was approximately 63% and the mean residence time was slightly enhanced via this administration route. T1/2=11.69±1.5, 9.67±0.2, and 9.37±0.5 hours for 10 mg/kg i.v., 10 mg/kg p.o., and 20 mg/kg p.o., respectively.
References & source
[1]. Le P, et al. Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms. Nat Chem. 2019 Dec 16.
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.