Mofezolac
(Synonyms: 莫苯唑酸) 目录号 : GC61843
A COX-1 inhibitor
Cas No.:78967-07-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Mofezolac is an inhibitor of COX-1 (IC50 = 14 nM).1 It is selective for COX-1 over COX-2 (IC50 = 440 nM). Mofezolac (1 ?g/ml) protects against LPS-induced cell death in BV-2 microglia. In vivo, mofezolac (6 mg/kg, i.p.) reduces hippocampal microglial activation and prostaglandin E2 production in a mouse model of LPS-induced neuroinflammation. It reduces phenylquinone-induced writhing in a mouse model of acute pain.2 Dietary administration of mofezolac (1,200 ppm) reduces the number of aberrant crypt foci and tumors in a rat model of beef tallow diet-induced colon carcinogenesis.3
1.Calvello, R., Lofrumento, D.D., Perrone, M.G., et al.Highly selective cyclooxygenase-1 inhibitors P6 and mofezolac counteract inflammatory state both in vitro and in vivo models of neuroinflammationFront. Neurol.8251(2017) 2.Goto, K., Ochi, H., Yasunaga, Y., et al.Analgesic effect of mofezolac, a non-steroidal anti-inflammatory drug, against phenylquinone-induced acute pain in miceProstaglandins Other Lipid Mediat.56(4)245-254(1998) 3.Miao, L., Shiraishi, R., Fujise, T., et al.Chemopreventive effect of mofezolac on beef tallow diet/azoxymethane-induced colon carcinogenesis in ratsHepatogastroenterology58(105)81-88(2011)
| Cas No. | 78967-07-4 | SDF | |
| 别名 | 莫苯唑酸 | ||
| Canonical SMILES | O=C(O)CC1=C(C2=CC=C(OC)C=C2)C(C3=CC=C(OC)C=C3)=NO1 | ||
| 分子式 | C19H17NO5 | 分子量 | 339.34 |
| 溶解度 | 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 | 2.9469 mL | 14.7345 mL | 29.469 mL |
| 5 mM | 0.5894 mL | 2.9469 mL | 5.8938 mL |
| 10 mM | 0.2947 mL | 1.4734 mL | 2.9469 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。
An attempt to chemically state the cross-talk between monomers of COX homodimers by double/hybrid inhibitors mofezolac-spacer-mofezolac and mofezolac-spacer-arachidonic acid
Eur J Med Chem 2021 Jan 1;209:112919.PMID:33129592DOI:10.1016/j.ejmech.2020.112919.
Cardiovascular diseases (CVDs) account for over 17 million death globally each year, including arterial thrombosis. Platelets are key components in the pathogenesis of this disease and modulating their activity is an effective strategy to treat such thrombotic events. Cyclooxygenase-1 (COX-1) isoenzyme is involved in platelet activation and is the main target of non-steroidal anti-inflammatory drugs (NSAIDs) and new selective inhibitor research. Inhibitors of general formula mofezolac-spacer-mofezolac (mof-spacer-mof) and mofezolac-spacer-arachidonic acid (mof-spacer-AA) were projected to investigate the possible cross-talk between the two monomers (Eallo and Ecat) forming the COX-1 homodimer. Mofezolac was chosen as either one or two moieties of these molecules being the known most potent and selective COX-1 inhibitor and administrated to humans as Disopain™, then arachidonic acid (AA) was used to develop molecules bearing, in the same compound, in addition to the inhibitor moiety (Mofezolac) also the natural COX substrate. Depending on the nature of the spacer, COX-1 and COX-2 activity was differently inhibited by mof-spacer-mof set with a preferential COX-1 inhibition. The highest COX-1 selectivity was exhibited by the compound in which the spacer was the benzidine [N,N'-(biphenyl-4,4'-di-yl)bis (2-[3,4-bis(4-methoxyphenyl)isoxazol-5-yl]acetamide) (15): COX-1 IC50 = 0.08 μM, COX-2 IC50 > 50 μM, Selectivity Index (SI) > 625]. In the case of mof-spacer-AA set, the COX inhibitory potency and also the isoform preference changed. (5Z, 8Z, 11Z, 14Z)-N-(4-{2-[3,4-Bis(4-methoxyphenyl)isoxazol-5-yl]acetamido}butyl)icosa-5,8,11,14-tetraenamide (19) and (5Z, 8Z, 11Z, 14Z)-N-(4'-{2-[3,4-bis(4-methoxyphenyl)isoxazol-5-yl]acetamido}-[1,1'-biphenyl]-4-yl)icosa-5,8,11,14-tetraenamide (21), in which the spacer is the 1,2-diaminobutane or benzidine, respectively, selectively inhibited the COX-2, whereas when the spacer is the 1,4-phenylendiamine [(5Z, 8Z, 11Z, 14Z)-N-(4-{2-[3,4-bis(4-methoxyphenyl)isoxazol-5-yl]acetamido}phenyl)icosa-5,8,11,14-tetraenamide) (20) the COX preference is COX-1 (COX-1 IC50 = 0.05 μM, COX-2 IC50 > 50 μM, with a COX-1 selectivity > 1000). Molecular modelling by using FLAP algorithm shows fundamental interactions of the novel compounds at the entry channel of COX and inside its catalytic cavity. The effect of these mof-spacer-mof and mof-spacer-AA in inhibiting in vitro free arachidonic acid-induced platelet aggregation was also determined. A positive profile of hemocompatibility in relation to their influence on the blood coagulation cascade and erythrocyte toxicity was observed. Cytotoxicity and genotoxicity safety were also found for these two novel sets of compounds.
Targeting COX-1 by mofezolac-based fluorescent probes for ovarian cancer detection
Eur J Med Chem 2019 Oct 1;179:16-25.PMID:31229884DOI:10.1016/j.ejmech.2019.06.039.
Biomarkers of specific targets are becoming an essential objective for clinical unmet clinical needs to improve diseases early detection and increase patient overall survival. Ovarian cancer is among the highest mortality gynecological cancers. It is asymptomatic and almost always diagnosed at advanced stage. At five years from the first diagnosis the survival rate of ovarian cancer patients is only 30%. Cyclooxygenase (COX)-1 as opposed to COX-2 is known to be overexpressed in ovarian cancer. Therefore, fluorescent probes targeting COX-1 were designed and prepared in fair to good yields for its quantitatively detection in human ovarian cancer cell lines (OVCAR-3 and SKOV-3). In particular, both cytofluorimetric and immunofluorescent experiments showed that N-[4-(9-dimethylimino-9H-benzo[a]phenoxazin-5-ylamino)butyl]-2-(3,4-bis(4-methoxyphenyl)isoxazol-5-yl)acetamide chloride (11) enters into OVCAR-3 cells and is mainly localized on the membrane containing the COX-1. Membrane fluorescence emission represents about 80% of the total fluorescence measured in the whole cell, while the non-specific labeling represents only 20%. This result indicates that the intensity of fluorescence emission is almost exclusively attributable to 11 bound to COX-1 located on the membrane. Furthermore, no diffusion inside the cell occurs. IC50hCOX-1 value of 11 determined by measuring the O2 consumption during the bis-oxygenation of the arachidonic acid catalysed by COX-1 was found to be equal to 1.8 nM. Furthermore, 11 inhibits oCOX-1 with IC50 = 6.85 nM and mCOX-2 with IC50 = 269.5 nM; the corresponding selectivity index SI is equal to 39.3 against oCOX-1. 11 inhibits oCOX-1 at 0 min of incubation with 91% inhibition, whereas in the same time it does not inhibit mCOX-2. Fingerprints for Ligands and Proteins (FLAP) software calculations were performed to justify 11 higher COX-1 inhibitory potency than Mofezolac (COX-1 IC50 = 5.1 nM), which in turn is a moiety of 11. Specifically, the two compounds bind differently in the COX-1 active site.
[Pharmacological profile of Mofezolac, a new non-steroidal analgesic anti-inflammatory drug]
Nihon Yakurigaku Zasshi 1990 Feb;95(2):63-81.PMID:2109726DOI:10.1254/fpj.95.2_63.
Pharmacological activities of Mofezolac were investigated in experimental animal models and compared with those of indomethacin, ibuprofen, mefenamic acid, aspirin and aminopyrine. Mofezolac showed a potent suppression of various writhing models in mice or rats; and its potency was slightly lower than that of indomethacin, but was higher than those of the other reference drugs. Thus, Mofezolac was especially active against chemically induced writhing and also in the phenylquinone induced intraperitoneal dye leakage reaction in mice. Mofezolac also has a potent inhibitory activity on the algesic responses induced by the mechanical stimulus of the inflammed tissue. Mofezolac exhibited a therapeutic effect comparable to indomethacin in the urate synovitis in dogs. Considering the anti-inflammatory and antipyretic actions, Mofezolac was obviously less effective than indomethacin, and its potency was similar to that of ibuprofen. The ulcerogenic effect of Mofezolac on the gastric mucosa was far weaker than that of indomethacin. In in vitro studies, the prostaglandin biosynthesis and platelet aggregation were inhibited to the same extent by both Mofezolac and indomethacin. Accordingly, it may be considered that the actions of Mofezolac are due to the inhibition of cyclooxygenase. Our result suggest that Mofezolac can be a useful drug that shows a rapid pain-relieving activity in acute inflammations.
Effect of mofezolac-galactose distance in conjugates targeting cyclooxygenase (COX)-1 and CNS GLUT-1 carrier
Eur J Med Chem 2017 Dec 1;141:404-416.PMID:29032033DOI:10.1016/j.ejmech.2017.09.066.
Neuroinflammation is the earliest stage of several neurological and neurodegenerative diseases. In the case of neurodegenerative disorders, it takes place about 15-20 years before the appearance of specific neurodegenerative clinical symptoms. Constitutive microglial COX-1 is one of the pro-inflammatory players of the neuroinflammation. Novel compounds 3, 14 and 15 (Galmof0, Galmof5 and Galmof11, respectively) were projected, and their synthetic methodologies developed, by linking by an ester bond, directly or through a C5 or C11 unit linker the highly selective COX-1 inhibitor Mofezolac (COXs selectivity index > 6000) to galactose in order to obtain substances capable to cross blood-brain barrier (BBB) and control the CNS inflammatory response. 3, 14 and 15 (Galmofs) were prepared in good to fair yields. Galmof0 (3) was found to be a selective COX-1 inhibitor (COX-1 IC50 = 0.27 μM and COX-2 IC50 = 3.1 μM, selectivity index = 11.5), chemically and metabolically stable, and capable to cross Caco-2 cell monolayer, resembling BBB, probing that its transport is GLUT-1-mediated. Furthermore, Galmof0 (3) powerfully inhibits PGE2 release higher than Mofezolac (1) in LPS-stimulated mouse BV2 microglial cell line, a worldwide recognized neuroinflammation model. In addition, Fingerprints for Ligands and Proteins (FLAP) was used to explain the different binding interactions of Galmofs with the COX-1 active site.
Analgesic effect of Mofezolac, a non-steroidal anti-inflammatory drug, against phenylquinone-induced acute pain in mice
Prostaglandins Other Lipid Mediat 1998 Jul;56(4):245-54.PMID:9777656DOI:10.1016/s0090-6980(98)00054-9.
The oral administration of Mofezolac, [3,4-di(4-methoxyphenyl)-5-isoxazolyl]acetic acid, resulted in the suppression of writhing induced by the intraperitoneal injection of phenyl-p-benzoquinone (phenylquinone, PQ) in mice. The analgesic activity of Mofezolac was almost as potent as that of indomethacin, and more potent than that of sodium diclofenac, zaltoprofen, NS-398, and etodolac when their 50% effective doses were compared. The in vitro inhibitory activity of Mofezolac against ovine cyclooxygenase (COX)-1 was also more potent than that of any other non-steroidal anti-inflammatory drugs (NSAIDs) tested, whereas the activity of Mofezolac against COX-2 was relatively weak. A Western analysis revealed COX-1 to be constitutively expressed, whereas COX-2 was hardly expressed until 30 min after the PQ-injection in the peritoneal cells. Because the writhing terminated within 30 min after PQ-injection, the prostaglandins involved in the induction of writhing seem to be derived from COX-1. These data thus indicate that potent analgesic activity of Mofezolac against the present model to be more closely related to its potent inhibitory activity against COX-1 but not against COX-2.