| (-)-MK 801NMDA antagonist,potent and selective |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
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- Purity = 99.95%
- COA (Certificate Of Analysis)
- HPLC
- NMR (Nuclear Magnetic Resonance)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
| In vitro experiment [1]: | |
Samples | Rat cortical slices |
Preparation method | The solubility of this compound in DMSO is > 10.3 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
Reacting condition | 75 nM; 2 hrs |
Applications | In rat cortical slices, (-)-MK 801 potently blocked N-Me-D-Asp-induced depolarizing responses. At the concentrations of 75 nM and above, (-)-MK 801 irreversibly inhibited N-Me-D-Asp responses and thus, the effect of (-)-MK 801 was persistent. However, (-)-MK 801 acted slowly, reaching its maximal effect only after 90 ~ 120 mins of continuous superfusion. |
| Animal experiment [2]: | |
Animal models | A rat model of ischemic spinal cord injury |
Dosage form | 1 mg/kg; i.v. |
Applications | In a rat model of ischemic spinal cord injury, (-)-MK 801 significantly improved neurological outcome and recovery. Moreover, histopathology results showed that (-)-MK 801 reduced injuries in the lumbar gray matter. These results demonstrated that a single dose of (-)-MK 801 given before ischemic spinal cord injury exerted significant neuroprotection effect. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Wong EH, Kemp JA, Priestley T, Knight AR, Woodruff GN, Iversen LL . The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7104-8. [2]. Kocaeli H, Korfali E, Oztürk H, Kahveci N, Yilmazlar S. MK-801 improves neurological and histological outcomes after spinal cord ischemia induced by transient aortic cross-clipping in rats. Surg Neurol. 2005;64 Suppl 2:S22-6; discussion S27. | |
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| Cas No. | 121917-57-5 | SDF | Download SDF |
| Chemical Name | (5R,10S)-5-methyl-10,11-dihydro-5H-5,10-epiminodibenzo[a,d][7]annulene | ||
| Canonical SMILES | C[C@@]1(N2)C3=C(C=CC=C3)C[C@H]2C4=C1C=CC=C4 | ||
| Formula | C16H15N | M.Wt | 221.30 |
| Solubility | ≥10.3mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
(+)-MK 801 Maleate is a potent antagonist of NMDA with Ki value of 30.5nM [1].
MK 801 is a potent anticonvulsant exhibits both anxiolytic and sympathomimetic properties. It is found to be a noncompetitive antagonist of NMDA. MK 801 can penetrate into the central nervous system. In the in vitro assay, MK 801 binds to rat cerebral cortical membrane with high affinity in a saturable manner. This binding is reversible even when the concentration of MK 801 is up to 100μM. It is also found that the binding shows a regional specificity. Most of these binding sites are located in the hippocampus. In rat cortical-slice preparations, MK 801 causes a potent blockade of depolarizing responses to NMDA with a high selectivity. This effect is persistent. The blockade can also cause a suppression of the epileptiform activity induced by tetrodotoxin or other neurotoxin [1].
References:[1] Wong EH, Kemp JA, Priestley T, Knight AR, Woodruff GN, Iversen LL . The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7104-8.
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⒈通过嵌入DNA双链的碱基之间，形成稳定复合物，抑制DNA复制与RNA合成，从而阻碍快速生长的癌细胞的分裂。
⒉抑制拓扑异构酶II，影响DNA超螺旋转化成为松弛状态，从而阻碍DNA复制与转录。有研究显示拓扑异构酶II抑制剂（除蒽环类药物还包括依托泊苷等）能够阻止拓扑异构酶II的翻转，而这点对于它从它的核酸底物上脱离是必需的。这就意味着，拓扑异构酶II抑制剂使拓扑异构酶II的复合物在DNA链断裂之后才能更稳定，导致后者催化了DNA的破坏；同时，拓扑异构酶II抑制剂还能阻碍连接酶对DNA的修复。
⒊螯合铁离子后产生自由基从而破坏DNA、蛋白质及细胞膜结构。向左转|向右转
我是新手。我要开始做实验了，但一开始就碰到了个很大的问题。
我想买个能利用哺乳动物细胞RNA聚合酶将DNA转录成RNA的的质粒，向好几家公司打了电话，但都没有我想要的东西。
没有这个东西，我的实验就只能是蓝图了。哪位战友有办法的，能不能帮帮我？
不胜感激。
伊立替康是喜树碱的半合成衍生物。喜树碱可特异性地与拓扑异构酶I结合，后者诱导可逆性单链断裂，从而使DNA双链结构解旋；伊立替康及其活性代谢物SN－38可与拓扑异构酶I－DNA复合物结合，从而阻止断裂单链的再连接。现有研究提示，伊立替康的细胞毒作用归因于DNA合成过程中，复制酶与拓扑异构酶I－DNA一伊立替康（或SN－38）三联复合物相互作用，从而引起DNA双链断裂。哺乳动物细胞不能有效地修复这种DNA双链断裂。
毒理研究
遗传毒性：伊立替康和SN－38在Ames试验中均未显示出致突变性。伊立替康在CHO细胞染色体畸变试验和小鼠微核试验中显示了致断裂作用。
生殖毒性：在啮齿动物多次给药试验中，可见雄性动物生殖器官萎缩。雌性大鼠静脉注射14C一伊立替康，其放射性可透过胎盘屏障，大鼠和家兔试验中，可见本品对胚胎和胎儿的毒性反应。大鼠静脉注射放射性标记的伊立替康后5分钟内，可在其乳汁中检测到放射性，给药4小时后乳汁中药物浓度可达到血药浓度的65倍；雌性大鼠在围产期静脉注射本品可引起仔鼠学习能力和雌鼠仔鼠体重的下降。
尚无足够的和严格控制的孕妇临床研究资料，若患者在孕期使用本品或在使用本品期间怀孕，应被告之对胎儿的潜在危害。有生育可能的妇女在本品给药期间应避免怀孕；母亲在接受本品治疗期间应停止哺乳。
致癌性：尚未进行伊立替康长期给药的致癌性研究，但进行了大鼠连续三周、每周一次静脉注射伊立替康2mg/kg和25mg/kg，然后恢复91周的试验（大鼠静脉注射伊立替康25mg/kg后，其Cmax和AUC分别约相当于人每周给药125mg/m2后的7倍和1.3倍）,结果显示，子宫喇叭口处子宫内膜间质息肉和子宫内膜间质肉瘤发生率的增加有明显的剂量依赖性。
【药代动力学】
文献报导，人体静脉注射本品后，伊立替康的血浆浓度呈常指数消除。平均消除半衰期为6～12小时，活性代谢产物SN－3 8的消除半衰期为10～20小时。因为其内酯和羟基酸是化学平衡的，故活性内酯和SN－38的半衰期与完整的伊立替康和SN－38的半衰期相近。
在50～350mg/m2的剂量范围内，伊立替康吸收面积（AUC）与剂量呈线性递增关系：SN－38的AUC增加要小于剂量的增加。在90分钟内静脉滴注本品后1小时内，活性代谢产物SN－38达到最大浓度。伊立替康与血浆蛋白的结合率为 30%～68%，明显低于SN－38与血浆蛋白的结合率（大约95%）。伊立替康主要在肝内由羧酸酯酶转化为活性代谢产物SN－38，后者代谢为葡萄糖甙酸，活性为SN－38的1/50～1/100（由体内细胞毒性检测）。体内分布不明；药物及代谢产物经尿排泄：伊立替康为11%～20%，SN－38<1%，SN－38糖甙约3%。给药48小时后胆汁蓄积和经尿排泄的药25%～50%。
【贮 藏】
遮光，密闭保存。
【包 装】
西林瓶装，1瓶/盒，有40mg及100mg两种规格。
效 期】
24个月
【执行标准】
WS1-（X-166）-2005Z
【生产企业】
企业名称：辉瑞制药；安万特制药；齐鲁制药；江苏恒瑞医药股份有限公司向左转|向右转
请规范发贴，求助贴请在标题前加【求助】，谢谢您的合作。——by草根
