S-methyl-KE-298 (M-2)
(Synonyms: M-2) 目录号 : GC31734
S-methyl-KE-298 (M-2) 是 KE-298 的活性代谢物。
Cas No.:143584-75-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
S-methyl-KE-298 is an active metabolite of KE-298. KE-298 inhibits matrix metalloproteinase (MMP-1) production from rheumatoid arthritis (RA) synovial cells.
S-methyl-KE-298 is a methyl conjugate of deacetyl-KE-298 is plasma[1]. In vitro protein binding of KE-298 and its plasma metabolites, deacetyl-KE-298 (M-1) and S-methyl-KE-298 (M-2), is high in rat (>97%), dog (>89%) and human plasma (>99%), respectively[2]. KE-298 blocks this IL-1β-induced pro-MMP-2 activation and MT1-MMP expression, but does not affect IL-1β-induced tissue inhibitor of metalloproteinase-2 (TIMP-2) secretion from rheumatoid synovial cells. KE-298 inhibits MMP-1 production from rheumatoid arthritis (RA) synovial cells by affecting a transcription factor, AP-1. KE-298 inhibits the basal levels of MT1-MMP expression of unstimulated rheumatoid synovial cells[3].
[1]. Yoshida H, et al. Identification of metabolites of KE-298, a new antirheumatic drug, and its physiological properties in rats. Biol Pharm Bull. 1996 Mar;19(3):424-9. [2]. Endo H, et al. Stereoselectivity and species difference in plasma protein binding of KE-298 and its metabolites. Biol Pharm Bull. 2001 Jul;24(7):800-5. [3]. Honda S, et al. Expression of membrane-type 1 matrix metalloproteinase in rheumatoid synovial cells. Clin Exp Immunol. 2001 Oct;126(1):131-6.
| Cas No. | 143584-75-2 | SDF | |
| 别名 | M-2 | ||
| Canonical SMILES | CSCC(C(O)=O)CC(C1=CC=C(C)C=C1)=O | ||
| 分子式 | C13H16O3S | 分子量 | 252.33 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Stereoselectivity and species difference in plasma protein binding of KE-298 and its metabolites
In vitro protein binding of KE-298 and its plasma metabolites, deacetyl-KE-298 (M-1) and S-methyl-KE-298 (M-2), was high in rat (>97%), dog (>89%) and human plasma (>99%), respectively. Human serum albumin (>93%) was the main protein involved in the binding to plasma proteins, while the binding to human serum globulins was low (16-33%). The binding of KE-298 and its metabolites in all species of plasma was stereoselective. The (+)-(S)-enantiomers of these compounds bound rat, dog and human plasma proteins to a greater extent than did the (-)-(R)-enantiomers, except that the case of KE-298 was opposite in rat plasma. The stereoselective plasma levels of these compounds in rats, dogs, or humans would likely be due to stereoselective differences in binding to plasma albumin. The protein binding of M-1 in adjuvant-induced arthritis rat plasma was >97%, and the stereoselectivity was similar to the case of normal rat plasma. KE-298 and its metabolites remarkably displaced [14C]warfarin, which bound on albumin in a solution of diluted rat serum albumin. Similarly, there was a displacement of [14C]warfarin in solutions of dog and human serum albumin, and concomitantly the displacement of [14C]diazepam. [3H]Digitoxin was not displaced by any of the enantiomers in each albumin solution. No stereoselectivity was found in displacement by enantiomers of the three compounds. These results suggest that stereoselective protein binding can be attributed to quantitative differences in binding to albumin rather than to the different binding sites.
Stereoselective disposition and chiral inversion of KE-298, a new antirheumatic drug, in rats
The present study was an attempt to elucidate the relationship between stereoselective pharmacokinetics and protein binding of KE-298 and its active metabolites, deacetyl-KE-298 (M-1) and S-methyl-KE-298 (M-2). Metabolic chiral inversion was also investigated. The levels of unchanged KE-298 in plasma after oral administration of (+)-(S)-KE-298 to rats were lower than those of (-)-(R)-KE-298, whereas the levels of M-1 and M-2 after administration of (+)-(S)-KE-298 were higher than after (-)-(R)-KE-298. In vitro, rat plasma protein binding of (+)-(S)-KE-298 was lower than that of (-)-(R)-KE-298. In contrast, the binding of (+)-(S)-M-1 and (+)-(S)-M-2 was higher than that of (-)-(R)-M-1 and (-)-(R)-M-2. Displacement studies revealed that the (+)-(S) and (-)-(R)- enantiomers of KE-298 and their metabolites bound to the warfarin binding site on rat serum albumin. These results suggested that the stereoselective plasma levels in KE-298 and its metabolites were closely related to enantiomeric differences in protein binding attributed to quantitative differences in binding to albumin rather than to the different binding sites. Unidirectional chiral inversion was detected after oral administration of either (-)-(R)-KE-298 or (-)-(R)-M-2 to rats both yielding (+)-(S)-M-2.