ML267
ML267 is a blood-brain barrier permeable Antibacterial agent and bacterial phosphopantetheinyl transferase (PPTase) inhibitor, with an IC50 of 0.29 μM against Bacillus subtilis Sfp-PPTase and an IC50 of 8.1 μM against bacterial AcpS-PPTase. ML267 attenuates bacterial secondary metabolism, activity, and the production of Sfp-PPTase-dependent metabolites. ML267 inhibits the growth of Gram-positive bacteria, including Methicillin (HY-121544)-resistant Staphylococcus aureus. ML267 is applicable to research related to bacterial infections, including methicillin-resistant Staphylococcus aureus infections.
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- No. CAS: 1542213-67-1
- Fòrmula: C19H18ClF6N5O3S
- Peso molecular:545.89
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Almacenamiento:
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Actividad biológica
Descripciòn
In Vitro
ML267 (3.6 nM-114 μM; 15 min pre-incubation, 30 min reaction) potently inhibits bacterial Sfp-PPTase with an IC50 of 0.290 μM and shows no activity against human PPTase at concentrations up to 114 μM[1].
ML267 (free base) (up to 8.1 μM; 15 min pre-incubation, 60 min reaction) inhibits bacterial AcpS-PPTase with an IC50 of 8.1 μM[1].
ML267 (0.4-100 μg/mL; 16-20 h, 4 h resazurin) exhibits bactericidal activity against Gram-positive bacterial strains including methicillin-resistant Staphylococcus aureus, with MICs ranging from 1.7 to 6.3 μg/mL, and no activity against Gram-negative bacteria or fungi[1].
ML267 (free base) (0.53-1.1 μg/mL; 28 h) dose-dependently attenuates Sfp-PPTase-dependent surfactin production in Bacillus subtilis OKB105 by 33-41% at sublethal concentrations, with minimal impact on bacterial growth[1].
ML267 potently inhibits bacterial Sfp-type PPTase (IC50 = 0.29 μM) and AcpS-type PPTase (IC50 = 8.1 μM), with no activity against the human PPTase ortholog[2].
ML267 (0.156-40 μM; 6 h) inhibits the growth of Bacillus subtilis ATCC 21332 with a MIC of 5.0 μM[2].
ML267 (15 min with enzyme, 30 min with substrate) potently inhibits Sfp phosphopantetheinyl transferase with an IC50 of 290 nM in a qHTS assay[3].
ML267 (48 h) exhibits no significant cytotoxicity against HepG2 human hepatocarcinoma cells, with an IC50 greater than 57 μM[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HepG2 human hepatocarcinoma cells
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Concentration:serial dilutions
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Incubation Time:48 h
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Result:Showed no significant cytotoxicity against HepG2 cells, with an IC50 greater than 57 μM.
In Vivo
ML267 (3-30 mg/kg; i.v., i.p.; single dose) achieves favorable systemic exposure and crosses the blood-brain barrier in healthy CD1 mice with no acute toxicity at tested doses[1].
ML267 (3-30 mg/kg; i.v., i.p.; single dose) exhibits favorable in vivo pharmacokinetic properties in male CD-1 mice, with 98.5% bioavailability after intraperitoneal administration at 30 mg/kg and a plasma-to-brain ratio of 2.1, and a half-life of 2.4 hours after intravenous administration at 3 mg/kg[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CD1 (male, 6−8 weeks of age)[1]
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Dosage:3 mg/kg (i.v.); 30 mg/kg (i.p.)
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Administration:i.v.; single dose; i.p.; single dose
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Result:Had a half-life (T1/2) of 2.4 h, maximum concentration (Cmax) of 4114 ng/mL, area under the curve (AUCinf) of 6983 h·ng/mL, volume of distribution (Vd) of 1.5 L/kg, mean residence time (MRT) of 3.4 h, clearance of 7.2 mL/min/kg, and plasma-to-brain ratio (P/B) of 2.5 following i.v. administration.
Had a half-life (T1/2) of 2.0 h, maximum concentration (Cmax) of 17633 ng/mL, area under the curve (AUCinf) of 68860 h·ng/mL, and plasma-to-brain ratio (P/B) of 2.1 following i.p. administration.
Noted no adverse clinical observations over 24 hours.
Chemical Information
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No. CAS 1542213-67-1
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Peso molecular 545.89
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Fòrmula C19H18ClF6N5O3S
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SMILES
S=C(N1CCN(C2=NC=C(C(F)(F)F)C=C2Cl)CC1)NC3=NC=CC(OC)=C3.O=C(O)C(F)(F)F
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Foley TL, et al. 4-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), a potent inhibitor of bacterial phosphopantetheinyl transferase that attenuates secondary metabolism and thwarts bacterial growth. J Med Chem. 2014 Feb 13;57(3):1063-78. [Content Brief]
[2]. Konno S, et al. A Chemoproteomics Approach to Investigate Phosphopantetheine Transferase Activity at the Cellular Level. Chembiochem. 2017;18(18):1855-1862. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ML267 Related Classifications
HY-137502 Related Classifications
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Keywords
- ML267
- 1542213-67-1
- ML 267
- ML-267
- Bacterial
- Escherichia coli BW25113
- nonribosomal peptide synthetases
- AcpS-PPTase
- phosphopantetheinyl transferase
- Bacillus subtilis Sfp-PPTase
- Candida albicans
- Gram-positive bacteria
- CD1 mice
- HepG2 human hepatocarcinoma cells
- methicillin-resistant Staphylococcus aureus
- Inhibitor
- inhibitor
- inhibit