| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
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| Other Sizes |
S-methyl-KE-298 is an active metabolite of KE-298, which is an inhibitor of matrix metalloproteinase (MMP-1) production from rheumatoid arthritis (RA) synovial cells.
| ln Vitro |
The methyl conjugate of deacetyl-KE-298 in plasma is known as S-Methyl-KE-298 [1]. In vitro protein binding of KE-298 in rats (>97%), dogs (>89%), and human plasma (>99%), and its plasma metabolites deacetyl-KE-298 (M-1) and S-methyl-KE-298 (M-2), respectively [2]. While KE-298 does not influence IL-1β-induced tissue inhibitor of metalloproteinase 2 (TIMP-2) secretion by rheumatoid synoviocytes, it does block IL-1β-induced pro-MMP-2 activation and MT1-MMP expression. By altering the transcription factor AP-1, KE-298 prevents rheumatoid arthritis (RA) synoviocytes from producing MMP-1. MT1-MMP expression at basal levels is inhibited by KE-298 in unstimulated rheumatoid synoviocytes [3].
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| ln Vivo |
In rats, following oral administration of KE-298 (5 mg/kg), S-methyl-KE-298 was detected as the second main metabolite in plasma, alongside the primary metabolite deacetyl-KE-298. The peak plasma level (\(C_{\text{max}}\)) of S-methyl-KE-298 was 5.0 μg/ml, which was reached between 10 to 30 minutes post-administration. The area under the concentration-time curve (\(AUC\)) for S-methyl-KE-298 was 15.6 μg·h/ml. [1]
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| Animal Protocol |
The animal experiment involved administering S-methyl-KE-298's parent drug, KE-298, to male Wistar rats (250-270 g). Animals were fasted overnight and up to 4 hours after drug administration. [¹⁴C]KE-298 or unlabeled KE-298 was administered orally as a suspension in 5% gum arabic. Blood samples were collected from the tail vein at various time points post-administration for analysis. For tissue distribution studies, rats were sacrificed under ether anesthesia at indicated times, and various tissues were collected. Urine and feces were collected using metabolic cages. [1]
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| ADME/Pharmacokinetics |
S-methyl-KE-298 is a methylated metabolite formed from deacetylated KE-298, which itself is the major deacetylated metabolite of KE-298. This S-methylation reaction is a common metabolic reaction of thiol-containing drugs. [1] In rat plasma, S-methyl-KE-298 is one of the major circulating metabolites after oral administration of KE-298. Its plasma concentration peaks early after administration (10-30 minutes) and remains detectable for up to 8 hours after administration. [1] The metabolic pathway of KE-298 is presumed to be: first, deacetylation to generate deacetylated KE-298, and then S-methylation of deacetylated KE-298 to generate S-methyl-KE-298. [1]
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| References |
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| Additional Infomation |
S-methyl-KE-298 was identified in rat plasma by thermal spray liquid chromatography-mass spectrometry (TSP LC-MS). Its mass spectrum showed (M+H)⁺ ions at m/z 253 and (M+NH₄)⁺ ions at m/z 270, which were 28 atomic mass units lower than the parent drug KE-298, consistent with the substitution of acetyl groups on the thioester by methyl groups. The identity of the compound was confirmed by comparison with synthetically prepared standards. [1]
Unlike the metabolism of some other thiol-containing drugs (such as D-penicillamine), no mixed disulfide of deacetylated-KE-298 with amino acids or drug disulfide dimers were detected after administration of KE-298, indicating that its metabolic pattern is different. [1] This study suggests that the rapid excretion of radioactive material and lack of tissue accumulation after administration of [¹⁴C]KE-298 may be partly due to the metabolic pathway of its thiol-containing metabolite (deacetyl-KE-298), including its conversion to S-methyl-KE-298, and its low responsiveness to protein binding. [1] |
| Molecular Formula |
C₁₃H₁₆O₃S
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|---|---|
| Molecular Weight |
252.33
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| Exact Mass |
252.082
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| CAS # |
143584-75-2
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| PubChem CID |
10037864
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
457.2±45.0 °C at 760 mmHg
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| Flash Point |
230.3±28.7 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.565
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| LogP |
2.84
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
17
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| Complexity |
270
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
WRIZBWMOURRWRW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H16O3S/c1-9-3-5-10(6-4-9)12(14)7-11(8-17-2)13(15)16/h3-6,11H,7-8H2,1-2H3,(H,15,16)
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| Chemical Name |
4-(4-methylphenyl)-2-(methylsulfanylmethyl)-4-oxobutanoic acid
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| Synonyms |
S-methyl-KE-298S-methyl-KE298
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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 (~396.31 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.91 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 (9.91 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 (9.91 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 | 3.9631 mL | 19.8153 mL | 39.6306 mL | |
| 5 mM | 0.7926 mL | 3.9631 mL | 7.9261 mL | |
| 10 mM | 0.3963 mL | 1.9815 mL | 3.9631 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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