| Identification | Back Directory | [Name]
PK150 | [CAS]
2165324-62-7 | [Synonyms]
PK150
Urea, N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-(2,2-difluoro-1,3-benzodioxol-5-yl)- | [Molecular Formula]
C15H8ClF5N2O3 | [MDL Number]
MFCD32667017 | [MOL File]
2165324-62-7.mol | [Molecular Weight]
394.68 |
| Chemical Properties | Back Directory | [Boiling point ]
322.1±42.0 °C(Predicted) | [density ]
1.63±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (up to at least 25 mg/ml). | [form ]
solid | [pka]
12.44±0.40(Predicted) | [color ]
White | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month. |
| Hazard Information | Back Directory | [Description]
PK150 (2165324-62-7) is a Sorafenib analog that displays significant antibacterial activity against several pathogenic strains (S.aureus?NCTC8325, MIC = 0.3 μM; vancomycin -resistant enterococci, MIC = 3 μM; and?M.tuberculosis?MIC = 2 μM). It was inactive against Gram-negative bacteria. It effectively reduced persister cells in ciprofloxacin-treated stationary?S.aureus?cultures and effectively eradicated staphylococcus biofilms. PK150 did not develop antibacterial resistance in an agar-plate-based assay. Its antibacterial properties were attributed to demethylmenaquinone methyltransferase (MenG) inhibition and signal peptidase IB (SpsB) activation. PK150 displayed?in vivo?efficacy in a murine bloodstream infection model against methicillin-sensitive?S. aureus?and a neutropenic mouse thigh model against methicillin-resistant?S. aureus?strain ATCC33591. Inactive against a panel of over 250 human kinases. | [Uses]
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 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]
1) Le?et al.?(2019)?Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms; Nat. Chem.?12?145 |
|
| Company Name: |
Rhawn Reagent
|
| Tel: |
400-400-1332688 18019345275 |
| Website: |
http://www.rhawn.cn |
| Company Name: |
InvivoChem
|
| Tel: |
13549236410 |
| Website: |
https://www.invivochem.cn/ |
| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
|