MDL 72527 dihydrochloride
(Synonyms: N1,N4-二(BUTA-2,3-二ENYL)丁烷-1,4-二胺双盐酸盐) 目录号 : GC10545MDL 72527 dihydrochloride是一种有效的多胺氧化酶（PAO）抑制剂。
Cas No.:93565-01-6
Sample solution is provided at 25 µL, 10mM.
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MDL 72527 dihydrochloride is a potent inhibitor of polyamine oxidase (PAO)[1]. PAO plays a crucial role in maintaining intracellular polyamine homeostasis by regulating the degradation of polyamines such as spermine and its acetylated forms[2]. MDL 72527 dihydrochloride is commonly used in studies investigating the role of polyamine metabolism in cancer, neuroprotective mechanisms, and the function of PAO in infection and hyperoxia models[3, 4].
In vitro, pretreatment of wild-type mouse platelets with MDL 72527 dihydrochloride (100μM) for 30min significantly attenuated the increase in cytosolic Ca2+ concentration induced by stimulation with 2μg/mL collagen-related peptide (CRP) for 100s[5]. In M14 WT cells, a 24 pretreatment with MDL 72527 dihydrochloride (300μM) followed by co-incubation with bovine serum amine oxidase (BSAO; 6.5×10-3IU/mL) and spermine (6μM) at 37℃ for 60min resulted in severe mitochondrial damage, including matrix dilution and cristae fragmentation[6].
In vivo, in a C57BL/6J mouse model of experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG), treatment with MDL 72527 dihydrochloride (20mg/kg; three times/week) starting from the first day post-induction for 36 days significantly reduced the clinical scores during this period, ameliorated EAE-induced motor deficits, and delayed the onset of paralysis[7]. In a C57BL/6J mouse model of oxygen-induced retinopathy (OIR) with hyperoxia exposure, daily intraperitoneal injection of MDL 72527 dihydrochloride (39mg/kg) from postnatal day 6 (P6) to postnatal day 12 (P12) significantly reduced the area of retinal vaso-obliteration and promoted vascular sprouting[8].
References:
[1] SEILER N, DURANTON B, RAUL F. The polyamine oxidase inactivator MDL 72527[J]. Progress in drug research, 2002: 1-40.
[2] WANG Y, DEVEREUX W, WOSTER P M, et al. Cloning and characterization of a human polyamine oxidase that is inducible by polyamine analogue exposure[J]. Cancer research, 2001, 61(14): 5370-5373.
[3] DOGAN A, RAO A M, HATCHER J, et al. Effects of MDL 72527, a specific inhibitor of polyamine oxidase, on brain edema, ischemic injury volume, and tissue polyamine levels in rats after temporary middle cerebral artery occlusion[J]. Journal of neurochemistry, 1999, 72(2): 765-770.
[4] PEGG A E. Toxicity of polyamines and their metabolic products[J]. Chemical research in toxicology, 2013, 26(12): 1782-1800.
[5] LIU G, CAO H, LIU G, et al. Effect of lysosomotropic polyamineoxidase inhibitor mdl-72527 on platelet activation[J]. Cellular Physiology and Biochemistry, 2016, 38(5): 1695-1702.
[6] AGOSTINELLI E, BELLI F, MOLINARI A, et al. Toxicity of enzymatic oxidation products of spermine to human melanoma cells (M14): sensitization by heat and MDL 72527[J]. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2006, 1763(10): 1040-1050.
[7] LIU F, ALFARHAN M, BAKER L, et al. Treatment with MDL 72527 ameliorated clinical symptoms, retinal ganglion cell loss, optic nerve inflammation, and improved visual acuity in an experimental model of multiple sclerosis[J]. Cells, 2022, 11(24): 4100.
[8] PATEL C, XU Z, SHOSHA E, et al. Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2016, 1862(9): 1628-1639.
MDL 72527 dihydrochloride是一种有效的多胺氧化酶（PAO）抑制剂[1]。PAO通过调节精胺及其乙酰化形式等多胺的降解，在维持细胞内多胺稳态方面至关重要[2]。MDL 72527 dihydrochloride通常用于多胺代谢在癌症中的作用、神经损伤保护机制以及PAO在感染与高氧模型中功能的研究[3,4]。
在体外，MDL 72527 dihydrochloride（100μM）预处理野生型小鼠血小板30min，显著减弱了2μg/mL胶原相关肽（CRP）刺激100s所诱导的胞质Ca2+浓度升高[5]。MDL 72527 dihydrochloride（300μM）预处理M14 WT细胞24h，再与牛血清胺氧化酶（BSAO; 6.5×10-3IU/mL）及精胺（6μM）在37℃下共同孵育60min，引起了严重的线粒体损伤，包括基质稀碎和嵴碎裂[6]。
在体内，MDL 72527 dihydrochloride（20mg/kg; three times/week）从诱导后第一天开始治疗由髓鞘少突胶质细胞糖蛋白（MOG）诱导引起的实验性自身免疫性脑脊髓炎（EAE）C57BL/6J小鼠36天，显著降低了在此期间的临床评分，改善了EAE引起的运动缺陷，并延迟了瘫痪症状的出现[7]。MDL 72527 dihydrochloride（39mg/kg）通过腹腔注射从出生后第6天（P6）至出生后第12天（P12）每日处理高氧暴露的氧诱导视网膜病变（OIR）C57/BL6J小鼠，显著减少了视网膜血管闭塞面积，并促进了血管出芽[8]。
| Cell experiment [1]: | |
Cell lines | Platelets from wild-type mice |
Preparation Method | Platelets isolated from wild-type mice were exposed for 30min to MDL 72527 dihydrochloride (100µM) with subsequent activation with CRP (2µg/mL).Flow cytometry was employed to estimate cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence. |
Reaction Conditions | 100μM; 30min |
Applications | Pretreatment of murine platelets with MDL 72527 dihydrochloride (100µM) for 30min significantly blunted the CRP (2µg/mL)-induced increase in cytosolic Ca2+ concentration ([Ca2+ ]i) within 100s. |
| Animal experiment [2]: | |
Animal models | OIR C57BL/6J mouse model |
Preparation Method | Utilized the OIR mouse model, administered polyamine oxidases inhibitor MDL 72527 dihydrochloride from P6 to P12 (39mg/kg/day) and assessed retinal vascular structure at different stages of hyperoxia, P9 and P12. Then performed flatmounting and visualized the blood vessels using Isolectin B4 staining, and analyzed vaso-obliteration area and vessel sprouts using NIH ImageJ software. |
Dosage form | 39mg/kg; once daily; 7 days (P6-P12); i.p. |
Applications | MDL 72527 dihydrochloride treatment significantly reduced the area of vaso-obliteration in the hyperoxia-treated retina while simultaneously increasing the number of vascular sprouts at P9 compared with the vehicle control. |
References: | |
| Cas No. | 93565-01-6 | SDF | |
| 别名 | N1,N4-二(BUTA-2,3-二ENYL)丁烷-1,4-二胺双盐酸盐 | ||
| 化学名 | N1,N4-di(buta-2,3-dien-1-yl)butane-1,4-diamine dihydrochloride | ||
| Canonical SMILES | C=C=CCNCCCCNCC=C=C.Cl.Cl | ||
| 分子式 | C12H20N2.2HCl | 分子量 | 265.23 |
| 溶解度 | DMF: slightly,DMSO: 0.33 mg/ml,PBS (pH 7.2): 10 mg/ml | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.7703 mL | 18.8516 mL | 37.7031 mL |
| 5 mM | 754.1 μL | 3.7703 mL | 7.5406 mL |
| 10 mM | 377 μL | 1.8852 mL | 3.7703 mL |
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