ML267 free base
Based on 1 Customer Validation
ML267 free base 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 free base attenuates bacterial secondary metabolism, activity, and the production of Sfp-PPTase-dependent metabolites. ML267 free base inhibits the growth of Gram-positive bacteria, including Methicillin (HY-121544)-resistant Staphylococcus aureus. ML267 free base is applicable to research related to bacterial infections, including methicillin-resistant Staphylococcus aureus infections.
For research use only. We do not sell to patients.
- Purity : 98.45%
- CAS No.: 1542213-03-5
- Formula: C17H17ClF3N5OS
- Molecular Weight:431.86
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Storage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HepG2 | IC50 |
114 μM
Compound: 55, ML267
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Cytotoxicity against human HepG2 cells assessed as cellular ATP content after 48 hrs by CellTiter-Glo assay
Cytotoxicity against human HepG2 cells assessed as cellular ATP content after 48 hrs by CellTiter-Glo assay
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[PMID: 24450337] |
In Vitro
ML267 (free base) (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 (free base) (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 (free base) 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 (free base) (0.156-40 μM; 6 h) inhibits the growth of Bacillus subtilis ATCC 21332 with a MIC of 5.0 μM[2].
ML267 (free base) (serial dilutions; 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 (free base) (serial dilutions; 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.
Parmacokinetics
| Species | Dose | Route | T1/2 | Cmax | AUCinf | Vd | MRT | CL | Bioavailability |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 3 mg/kg | i.v. | 2.4 h | 4114 ng/mL | 6983 ng·h/mL | 1.5 L/kg | 3.4 h | 7.2 mL/min/kg | / |
| Mice[1] | 30 mg/kg | i.p. | 2.0 h | 17633 ng/mL | 68860 ng·h/mL | / | / | / | / |
| Mice[3] | 3 mg/kg | i.v. | 2.4 h | / | 6983 ng·h/mL | 1.5 L/kg | 3.4 h | 7.2 mL/min/kg | / |
| Mice[3] | 30 mg/kg | i.p. | 2.0 h | 17633 ng/mL | 68860 ng·h/mL | / | / | / | 98.5 % |
In Vivo
ML267 free base (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 free base (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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CAS No. 1542213-03-5
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Appearance Solid
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Molecular Weight 431.86
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Formula C17H17ClF3N5OS
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Color White to off-white
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SMILES
FC(F)(C1=CN=C(N2CCN(CC2)C(NC3=NC=CC(OC)=C3)=S)C(Cl)=C1)F
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (231.56 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (278 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[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]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3156 mL | 11.5778 mL | 23.1557 mL | 57.8891 mL |
| 5 mM | 0.4631 mL | 2.3156 mL | 4.6311 mL | 11.5778 mL | |
| 10 mM | 0.2316 mL | 1.1578 mL | 2.3156 mL | 5.7889 mL | |
| 15 mM | 0.1544 mL | 0.7719 mL | 1.5437 mL | 3.8593 mL | |
| 20 mM | 0.1158 mL | 0.5789 mL | 1.1578 mL | 2.8945 mL | |
| 25 mM | 0.0926 mL | 0.4631 mL | 0.9262 mL | 2.3156 mL | |
| 30 mM | 0.0772 mL | 0.3859 mL | 0.7719 mL | 1.9296 mL | |
| 40 mM | 0.0579 mL | 0.2894 mL | 0.5789 mL | 1.4472 mL | |
| 50 mM | 0.0463 mL | 0.2316 mL | 0.4631 mL | 1.1578 mL | |
| 60 mM | 0.0386 mL | 0.1930 mL | 0.3859 mL | 0.9648 mL | |
| 80 mM | 0.0289 mL | 0.1447 mL | 0.2894 mL | 0.7236 mL | |
| 100 mM | 0.0232 mL | 0.1158 mL | 0.2316 mL | 0.5789 mL |
ML267 free base Related Classifications
HY-137502A Related Classifications
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Keywords
- ML267
- 1542213-03-5
- 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