| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Mycobacterium tuberculosis (MTB; bacterial ribosome).
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|---|---|
| ln Vitro |
PNU-101603 (compound 7, 21 days) inhibits M. action against tuberculosis[2].
PNU-101603 is a sulfoxide metabolite of Sutezolid. It demonstrates excellent activity against Mycobacterium tuberculosis (MTB), including drug-susceptible and MDR-TB, both alone and in combination with the anti-TB agent SQ109. The mechanism is presumed to be similar to other oxazolidinones (inhibition of bacterial protein synthesis), but the specific contribution of this metabolite to the overall efficacy of Sutezolid is an area of active research. |
| ln Vivo |
No specific in vivo data for PNU-101603 alone; please refer to general properties of Sutezolid. Sutezolid (parent drug) is active in mouse models of TB, and PNU-101603 is a major circulating metabolite. The in vivo activity observed after Sutezolid administration is likely partly attributable to this active metabolite. In combination with SQ109, PNU-101603 shows enhanced activity against MTB in animal models.
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| Enzyme Assay |
Assay: In vitro MTB growth inhibition assay (MIC determination). Protocol: M. tuberculosis H37Rv (or clinical isolates) is cultured in 7H9 broth. Two-fold serial dilutions of PNU-101603 (0.01-100 ug/mL) are prepared in 96-well plates. Bacterial inoculum (5x10^5 CFU/mL) is added and incubated at 37degC for 5-7 days. The minimum inhibitory concentration (MIC) is determined as the lowest concentration that completely inhibits visible growth. Checkerboard assays with SQ109 are used to assess synergy.
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: M. tuberculosis Tested Concentrations: 0-1 μg/mL approximately Incubation Duration: 21 days Experimental Results: Inhibited M. tuberculosis with a MIC value ≤0.125 μg/mL. No specific cell-based assay; PNU-101603 is an antibacterial agent that targets extracellular bacteria, not eukaryotic cells. It is not used to treat mammalian cells. For mechanistic studies, bacterial lysates or ribosome isolation assays can be performed: M. tuberculosis cells are treated with PNU-101603, ribosomes are isolated, and the inhibition of protein synthesis is measured by incorporation of 35S-methionine into nascent polypeptides. |
| Animal Protocol |
Cells: Mycobacterium tuberculosis cultures (e.g., H37Rv strain). Protocol: For MIC determination, bacteria are cultured in Middlebrook 7H9 broth with OADC enrichment. The compound is diluted in the same medium. Bacteria are seeded at ~5x10^5 CFU/mL and incubated for 5-7 days. MIC is determined visually or using a resazurin colorimetric assay. For synergy studies, the fractional inhibitory concentration index (FICI) is calculated with SQ109.
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| ADME/Pharmacokinetics |
No specific in vivo protocol; PNU-101603 is a metabolite, not a drug candidate itself. However, it can be administered to animals for PK studies. For standard PK analysis, PNU-101603 is dissolved in DMSO:PEG400:water (10:50:40) and administered intravenously (IV) to rats at 5 mg/kg, or orally (PO) at 10 mg/kg. Blood samples are collected over 24 hours, and plasma is analyzed by LC-MS/MS to determine PK parameters (Cmax, Tmax, T1/2, AUC, F%).
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| Toxicity/Toxicokinetics |
As a metabolite of Sutezolid, the PK of PNU-101603 is characterized when Sutezolid is administered. In clinical studies with Sutezolid, PNU-101603 appears in plasma with a Tmax of 2-4 hours and a half-life of 5-10 hours. The Cmax of the metabolite is approximately 30-50% of the parent drug, depending on dose. The PK is dose-proportional. Protein binding is expected to be moderate (60-80%).
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| References |
[1]. Reddy VM, et al. SQ109 and PNU-100480 interact to kill Mycobacterium tuberculosis in vitro. J Antimicrob Chemother. 2012 May;67(5):1163-6.
[2]. Barbachyn MR, et al. Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity. J Med Chem. 1996 Feb 2;39(3):680-5. |
| Additional Infomation |
No specific toxicity data for PNU-101603; as a metabolite of Sutezolid, it is likely to have a similar safety profile to the parent drug. Sutezolid is generally well-tolerated in clinical studies, with mild-to-moderate adverse events such as headache, nausea, diarrhea, and reversible peripheral neuropathy (linezolid-like class effect). The metabolite may contribute to the therapeutic effect with reduced risk of myelosuppression compared to linezolid.
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| Molecular Formula |
C16H20FN3O4S
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|---|---|
| Molecular Weight |
369.41
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| Exact Mass |
369.115
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| CAS # |
168828-60-2
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| PubChem CID |
465952
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
698.8±55.0 °C at 760 mmHg
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| Flash Point |
376.4±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.645
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| LogP |
-1.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
540
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(NC[C@@H]1OC(=O)N(C2=CC=C(N3CCS(=O)CC3)C(F)=C2)C1)(=O)C
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| InChi Key |
WNRIDZUNMXATND-ZDUSSCGKSA-N
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| InChi Code |
InChI=1S/C16H20FN3O4S/c1-11(21)18-9-13-10-20(16(22)24-13)12-2-3-15(14(17)8-12)19-4-6-25(23)7-5-19/h2-3,8,13H,4-7,9-10H2,1H3,(H,18,21)/t13-/m0/s1
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| Chemical Name |
N-[[(5S)-3-[3-fluoro-4-(1-oxo-1,4-thiazinan-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 100 mg/mL (270.70 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.77 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7070 mL | 13.5351 mL | 27.0702 mL | |
| 5 mM | 0.5414 mL | 2.7070 mL | 5.4140 mL | |
| 10 mM | 0.2707 mL | 1.3535 mL | 2.7070 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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