Marimastat是一种广谱的，具有口服活性的基质金属蛋白酶（MMP）抑制剂，IC50值为3~13nM。
Cas No.:154039-60-8
Sample solution is provided at 25 µL, 10mM.
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Marimastat is a broad-spectrum, orally active matrix metalloproteinase (MMP) inhibitor with IC50 values ranging from 3 to 13nM[1]. MMPs are a family of zinc-dependent proteolytic enzymes that are essential for tissue repair and remodeling, and are involved in various physiological processes including wound healing, angiogenesis, and cell migration[2]. Marimastat exerts its effects by inhibiting tumor metastasis and angiogenesis, and is commonly used in the research and treatment of pancreatic and gastric cancers[3,4].
In vitro, rat hippocampal neurons cultured in vitro on 7 days were pretreated with Marimastat (5nM, 0.5, 5, 40, and 100μM) for 30min, followed by stimulation with glutamate (50μM) for an additional 30min. Marimastat at 0.5μM inhibited MMP-9-dependent nectin-3 cleavage, while complete inhibition of nectin-3 cleavage was achieved at 5μM[5].
In vivo, C57BL/6J mice were administered Marimastat (100mg/kg; twice daily) by oral gavage for 1 week, followed by continued drug administration concomitant with CCl4 treatment for 6 weeks. Compared with the control group, the relative collagen content (hydroxyproline) in the liver increased by 25%, and the relative fibrotic area increased from 3.1% to 4.2%[6]. C57BL/6 mice fed a 60% high-fat diet for 9 weeks to induce hepatic steatosis were then treated with Marimastat (100mg/kg; twice daily) by oral gavage for 2 weeks, which significantly reduced fasting blood glucose levels[7].
References:
[1] RASMUSSEN H S, MCCANN P P. Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat[J]. Pharmacology & Therapeutics, 1997, 75(1): 69-75.
[2] NAGASE H, VISSE R, MURPHY G. Structure and function of matrix metalloproteinases and TIMPs[J]. Cardiovascular Research, 2006, 69(3): 562-573.
[3] KIMATA M, OTANI Y, KUBOTA T, et al. Matrix metalloproteinase inhibitor, marimastat, decreases peritoneal spread of gastric carcinoma in nude mice[J]. Japanese Journal of Cancer Research, 2002, 93(7): 834-841.
[4] STEWARD W P. Marimastat (BB2516): current status of development[J]. Cancer Chemotherapy and Pharmacology, 1999, 43(Suppl 1): S56-S60.
[5] PIJET B, KONOPKA A, REJMAK E, et al. The matrix metalloproteinase inhibitor marimastat inhibits seizures in a model of kainic acid-induced status epilepticus[J]. Scientific Reports, 2020, 10(1): 21314.
[6] DE MEIJER V E, SVERDLOV D Y, POPOV Y, et al. Broad-spectrum matrix metalloproteinase inhibition curbs inflammation and liver injury but aggravates experimental liver fibrosis in mice[J]. PLoS One, 2010, 5(6): e11256.
[7] DE MEIJER V E, LE H D, MEISEL J A, et al. Tumor necrosis factor α-converting enzyme inhibition reverses hepatic steatosis and improves insulin sensitivity markers and surgical outcome in mice[J]. PLoS One, 2011, 6(9): e25587.
Marimastat是一种广谱的，具有口服活性的基质金属蛋白酶（MMP）抑制剂，IC50值为3~13nM[1]。MMP是一类依赖锌的蛋白水解酶，对组织修复和重塑至关重要，参与了包括伤口愈合、血管生成和细胞迁移等生理过程[2]。Marimastat通过抑制肿瘤转移和血管生成发挥作用，通常用于胰腺癌和胃癌的研究和治疗[3,4]。
在体外，Marimastat（5nM, 0.5, 5, 40, and 100μM）预处理在体外培养了7天的大鼠海马神经元30min，然后加入谷氨酸（50μM）继续刺激30min，0.5μM的Marimastat即可抑制MMP-9依赖性的nectin-3切割，而在5μM浓度下则可完全抑制nectin-3切割[5]。
在体内，Marimastat（100mg/kg; twice daily）通过口服灌胃给药C57BL/6J小鼠1周，后在继续给药的同时用CCl4处理6周，较对照组肝脏相对胶原含量（羟脯氨酸）增加25%，相对纤维化面积从3.1%增加至4.2%[6]。C57BL/6小鼠经60%高脂饮食喂养9周诱导肝脂肪变性后，给予Marimastat（100mg/kg; twice daily）口服灌胃治疗2周，显著降低了空腹血糖水平[7]。
| Cell experiment [1]: | |
Cell lines | Hippocampal neurons (cultured in vitro on 7 days (DIV7)) |
Preparation Method | Rat hippocampal neurons were pretreated with Marimastat (5nM, 0.5, 5, 40, or 100μM) for 30min and then stimulated with glutamate (50μM) for an additional 30min, after which MMP-9-dependent cleavage of nectin-3 was assessed by immunoblotting, as indicated by the accumulation of the 17kDa proteolytic fragment. |
Reaction Conditions | 5nM, 0.5, 5, 40, or 100μM; 30min and additional 30min |
Applications | 0.5μM of Marimastat can inhibit MMP-9-dependent nectin-3 cleavage, while 5μM concentration can completely inhibit nectin-3 cleavage. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice with high-fat diet-induced hepatic steatosis |
Preparation Method | C57BL/6 mice were fed a 60% high-fat diet for 9 weeks to induce hepatic steatosis, then treated with Marimastat (100mg/kg; twice daily) via orogastric gavage for 2 weeks. At the end of the feeding experiments, mice were fasted for 6h. Glucose concentration was determined from tail vein blood. |
Dosage form | 100mg/kg; twice daily; 2 weeks; i.g. |
Applications | Treatment with Marimastat significantly reduced fasting blood glucose levels in mice with high-fat diet-induced hepatic steatosis. |
References: | |
| Cas No. | 154039-60-8 | SDF | |
| 别名 | 马立马司他; BB2516; TA2516 | ||
| 化学名 | (2R,3S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-N',3-dihydroxy-2-(2-methylpropyl)butanediamide | ||
| Canonical SMILES | CC(C)CC(C(C(=O)NO)O)C(=O)NC(C(=O)NC)C(C)(C)C | ||
| 分子式 | C15H29N3O5 | 分子量 | 331.41 |
| 溶解度 | ≥ 80.1 mg/mL in DMSO, ≥ 20.43 mg/mL in EtOH, ≥ 2.8 mg/mL in Water with ultrasonic and warming | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0174 mL | 15.0871 mL | 30.1741 mL |
| 5 mM | 603.5 μL | 3.0174 mL | 6.0348 mL |
| 10 mM | 301.7 μL | 1.5087 mL | 3.0174 mL |
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动物平均体重 | g | |
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动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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