PGS-IN-1 (KME-4)
(Synonyms: KME-4) 目录号 : GC32038
PGS-IN-1 (KME-4) 是一种有效的前列腺素合成酶 (PGS) 抑制剂，IC50 为 0.28 μM;也抑制 5-脂氧合酶，IC50 为 1.05 μM.
Cas No.:102271-49-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | PGS-IN-1 is dissolved in ethanol and the final concentration of ethanol is kept at 2% in each assay. The reaction mixture includes reaction buffer, enzyme (20 μg protein), and PGS-IN-1 in a total volume of 0.2 mL. The mixture is incubated for 15 min at 37°C with shaking and terminated by the addition of 2.5 mL ethyl acetate and 25 μL 1 N formic acid[1]. |
Animal experiment: | Rats: PGS-IN-1 is administered orally to groups of 4-6 male Wistar rats weighting 160-220 g. One hour later, 1 % carrageenin in 0.9 % NaCl is injected subcutaneously into a hind paw. Paw volumes are measured 5 h after the injection[1]. |
References: [1]. Katsumi I, et al. Studies on styrene derivatives. I. Synthesis and antiinflammatory activities of alpha-benzylidene-gamma-butyrolactone derivatives. Chem Pharm Bull (Tokyo). 1986 Jan;34(1):121-9. | |
PGS-IN-1 is a potent inhibitor of prostaglandin synthetase (PGS) with an IC50 of 0.28 μM; also inhibits 5-lipoxygenase with an IC50 of 1.05 μM.
The synthesized α-benzulidene-γ-butyrolactones are pure isomers (either cis or trans). PGS-IN-1 is the trans isomer. PGS-IN-1 exhibits potent antiinflammatrory and PGS inhibitory activity (IC50=0.28 μM). PGS-IN-1 also shows potent inhibitory activity against 5-lipoxygenase (IC50=1.05 μM)[1].
[1]. Katsumi I, et al. Studies on styrene derivatives. I. Synthesis and antiinflammatory activities of alpha-benzylidene-gamma-butyrolactone derivatives. Chem Pharm Bull (Tokyo). 1986 Jan;34(1):121-9.
| Cas No. | 102271-49-8 | SDF | |
| 别名 | KME-4 | ||
| Canonical SMILES | O=C1OCC/C1=C\C2=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C2 | ||
| 分子式 | C19H26O3 | 分子量 | 302.41 |
| 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 | 3.3068 mL | 16.5338 mL | 33.0677 mL |
| 5 mM | 0.6614 mL | 3.3068 mL | 6.6135 mL |
| 10 mM | 0.3307 mL | 1.6534 mL | 3.3068 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。
Analgesic and anti-inflammatory activities in rats of alpha-(3,5-di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), and its intestinal damage
alpha-(3,5-Di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), an anti-inflammatory drug, possesses analgesic activity in rat models. In the acetic acid-induced writhing test, the oral ED50 values for KME-4, indomethacin, naproxen and ibuprofen were 5.2, 3.8, 7.0 and 18.6 mg kg-1, respectively, and the relative order of potency of these drugs correlated with their inhibitory effect on acetic acid-induced vascular permeability in rats. KME-4 also had analgesic activity in the tests of Randall-Selitto and adjuvant arthritic flexion, but the dose required was greater than that needed in the writhing test. KME-4 (10 mg kg-1 day-1 orally) has a preventive effect against adjuvant-induced arthritis in rats, and its efficacy was more potent than indomethacin (2 mg kg-1 day-1) as judged from various parameters determined. When administered orally to rats once daily for 12 days, KME-4 caused perforating ulceration of the small intestine but this action was less potent than the effect of indomethacin, naproxen and ibuprofen.
Effect of alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory drug, on the established adjuvant arthritis in rats
The effect of alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory drug, on established adjuvant arthritis in rats was compared to that of indomethacin. When administered orally daily from days 14 to 27 starting on day 14 after the adjuvant (day 0), KME-4 (2 to 10 mg/kg) produced a dose-related reduction of the swelling of both injected and uninjected hindpaws, and it retarded body weight loss. The initiation of paw swelling after the cessation of therapy was not observed at either 5 mg/kg or 10 mg/kg of KME-4. On day 42 (15 days after discontinuation of dosing), KME-4 caused the recovery of organ weight, erythrocyte sedimentation rate (ESR) and serum albumin/globulin (A/G) ratio towards normal levels, and it also decreased radiographic bone damage scores in a dose-dependent manner. The results indicate that KME-4 produces the improvement of systemic symptoms in the established adjuvant arthritis. The results obtained with indomethacin were similar to those with KME-4. However, the degree of the efficacy of indomethacin (2 mg/kg) was lower than that of KME-4 (10 mg/kg) as judged by the measured parameters (ESR, serum A/G ratio and bone damage).
The effect of alpha-(3,5-di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory drug, on leucocyte migration in rat carrageenan pleurisy
KME-4,alpha-(3,5-di-t-butyl-4-hydroxybenzylidene)-gamma-buty rolactone was found to reduce the accumulation of leucocytes and exudate volume in the rat carrageenan pleurisy model. When administered orally 1 h before carrageenan, KME-4 (3-10 mg kg-1) induced a degree of inhibition of leucocyte migration almost equal to that of indomethacin (3-10 mg kg-1) in both 5 h and 24 h pleurisies. Furthermore, KME-4, when administered orally 5 h after the carrageenan, inhibited both monocyte numbers and exudate volume in a 24 h pleurisy and was more effective than indomethacin and BW755c which inhibited only monocyte migration. These results suggest that KME-4 has a differential anti-inflammatory activity. Dexamethasone (0.25 mg kg-1) showed strong inhibition of total cell numbers and exudate volume.
Pharmacological properties of a new anti-inflammatory compound, alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolacto ne (KME-4), and its inhibitory effects on prostaglandin synthetase and 5-lipoxygenase
The pharmacological effects of a new anti-inflammatory compound, alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), and its inhibitory effects on arachidonate prostaglandin synthetase and 5-lipoxygenase activities were examined. KME-4 showed anti-inflammatory activity. It was less active than indomethacin, but more active than naproxen and ibuprofen in carrageenin-induced paw edema in rats; and it was less active than indomethacin, equipotent as naproxen, but more active than ibuprofen in granuloma formation in rats. The ulcerogenic activity of KME-4 was weaker than indomethacin and naproxen, but stronger than ibuprofen in starved rats. The ratio of UD50 stomach to ED30 carrageenin edema or to ED25 granuloma for KME-4 showed higher values than those of the reference drugs. KME-4 showed antipyretic activity in yeast-induced fever in rats. It also inhibited platelet aggregation induced by arachidonic acid and protected rabbits from arachidonic acid-induced death. Furthermore, KME-4 was found to be equipotent in inhibiting both prostaglandin synthetase and 5-lipoxygenase activities of rat basophilic leukemia cells, unlike indomethacin, naproxen and ibuprofen. It also inhibited the prostaglandin synthetase activity of bovine seminal vesicle. The present findings indicate that KME-4 may be a new type of anti-inflammatory drug with dual prostaglandin synthetase and 5-lipoxygenase inhibition.
Inhibition of polymorphonuclear leukocyte 5-lipoxygenase and platelet cyclooxygenase by alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolacto ne (KME-4), a new anti-inflammatory drug
The effect of alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory compound, on arachidonate lipoxygenase and cyclooxygenase was investigated. KME-4 showed a dose-dependent inhibition of 5-lipoxygenase activity in both the cytosol (IC50: 0.85 microM) and ionophore A23187-stimulated cells (IC50: 11.5 microM) of guinea pig peritoneal polymorphonuclear leukocytes. KME-4 was also found to inhibit rabbit platelet cyclooxygenase (IC50: 0.44 microM), but had no inhibitory effect on platelet 12-lipoxygenase at concentrations up to 100 microM, whereas BW755C inhibited both enzymes in the same range of concentrations. The results indicate that KME-4 is a dual 5-lipoxygenase and cyclooxygenase inhibitor which is different from BW755C in affecting 12-lipoxygenase. These effects may provide information for understanding the pharmacological activity of KME-4.