CAS:905579-51-3
Storage:Powder:-20℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:Off-white to yellow Solid
MLN4924 是一种有效,选择性的NEDD8 活化酶 (NAE) 抑制剂。
Array ( [133] => Array ( [id] => 133 [name] => Inhibitors & Antagonists & Agonists [num] => [children] => Array ( [352] => Array ( [id] => 352 [name] => Protein Tyrosine Kinase/PTK ) [350] => Array ( [id] => 350 [name] => PI3K/Akt/mTOR ) [351] => Array ( [id] => 351 [name] => Endocrinology & Hormones ) [357] => Array ( [id] => 357 [name] => Angiogenesis ) [358] => Array ( [id] => 358 [name] => HIF ) [363] => Array ( [id] => 363 [name] => Immunology & Inflammation ) [364] => Array ( [id] => 364 [name] => Stem Cells ) [365] => Array ( [id] => 365 [name] => Apoptosis ) [377] => Array ( [id] => 377 [name] => Metabolic Enzyme & Protease ) [379] => Array ( [id] => 379 [name] => Autophagy ) [380] => Array ( [id] => 380 [name] => ER Stress ) [384] => Array ( [id] => 384 [name] => Cell Cycle ) [385] => Array ( [id] => 385 [name] => Cytoskeleton ) [386] => Array ( [id] => 386 [name] => DNA Damage & DNA Repai ) [387] => Array ( [id] => 387 [name] => Epigenetics ) [388] => Array ( [id] => 388 [name] => Ubiquitin ) [389] => Array ( [id] => 389 [name] => JAK/STAT ) [390] => Array ( [id] => 390 [name] => GPCR & G Protein ) [391] => Array ( [id] => 391 [name] => Neuronal Signal Pathway ) [392] => Array ( [id] => 392 [name] => MAPK ) [393] => Array ( [id] => 393 [name] => NF-κB ) [394] => Array ( [id] => 394 [name] => Membrane Transporter & Ion Channel ) [395] => Array ( [id] => 395 [name] => TGF-β/Smad ) [396] => Array ( [id] => 396 [name] => Hippo ) [775] => Array ( [id] => 775 [name] => Antibody-drug Conjugate/ADC Related ) [122] => Array ( [id] => 122 [name] => Others ) ) ) )
>
Small Molecule Compounds >
Inhibitors & Antagonists & Agonists >
Metabolic Enzyme & Protease >
mLN 4924CAS:905579-51-3
Storage:Powder:-20℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:Off-white to yellow Solid
CAS | 905579-51-3 |
English Name | mLN 4924 |
Synonyms | Pevonedistat |
Molecular Formula | C21H25N5O4S |
Molecular Weight | 443.52 |
Solubility | Soluble in DMSO |
Purity | ≥98% |
Appearance | Off-white to yellow Solid |
Storage | Powder:-20℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
MDL | MFCD00006838 |
SMILES | O=S(OC[C@@H]1C[C@@H](N2C3=NC=NC(N[C@H]4CCC5=C4C=CC=C5)=C3C=C2)C[C@@H]1O)(N)=O |
InChIKey | MPUQHZXIXSTTDU-QXGSTGNESA-N |
InChI | InChI=1S/C21H25N5O4S/c22-31(28,29)30-11-14-9-15(10-19(14)27)26-8-7-17-20(23-12-24-21(17)26)25-18-6-5-13-3-1-2-4-16(13)18/h1-4,7-8,12,14-15,18-19,27H,5-6,9-11H2,(H2,22,28,29)(H,23,24,25)/t14-,15+,18-,19-/m0/s1 |
PubChem CID | 16720766 |
Target Point | NAE |
Passage | Ubiquitin |
Background | mLN4924 is a potent and selective NEDD8 activating enzyme (NAE) inhibitor. |
Biological Activity | MLN4924 是一种有效,选择性的NEDD8 活化酶 (NAE) 抑制剂,IC50 为 4.7 nM[1]。 |
IC50 | 4.7nM(NAE)[1] |
In Vitro | 在纯化的酶和细胞测定中,与紧密相关的遍在蛋白激活酶(UAE,也称为UBA1)和SUMO激活酶(SAE; SAE1和UBA2亚基的异二聚体)相比,MLN4924选择性地抑制NAE活性。 MLN4924对多种人类肿瘤来源的细胞系具有强烈的细胞毒活性[1]。 |
In Vivo | MLN4924(sc,10 mg/kg,30 mg/kg或60 mg/kg)抑制NEDD8通路,导致携带HCT-116异种移植物的小鼠DNA损伤[1] .Pevonedistat(sc,120 mg/kg)和TNF -α(10μg/ kg)协同引起SD大鼠肝损伤[2]。 |
Cell Experiment | 将生长在6孔细胞培养皿中的HCT-116细胞用0.1%DMSO(对照)或0.3μMMLN4924处理24小时。制备全细胞提取物并通过免疫印迹分析。为了分析E2-UBL硫酯水平,通过非还原性SDS-PAGE分离裂解物,并用针对Ubc12,Ubc9和Ubc10的多克隆抗体进行免疫印迹。对于其他蛋白质的分析,通过还原SDS-PAGE分离裂解物并用如下一抗探测:针对CDT1,p27,孪蛋白,遍在蛋白,securin/PTTG和p53的小鼠单克隆抗体或针对NRF2,Cyclin B1和GADD34的兔多克隆抗体[1]。 |
Animal Experiment | 小鼠[1]给予300-500mm 3的HCT-116肿瘤的小鼠单次MLN4924剂量(10,30或60mg/kg),并在随后的24小时内在不同时间点切除肿瘤。使用Alexa680标记的抗-IgG作为二抗,通过定量免疫印迹分析估计NEDD8- cullin和NRF2的相对水平。使用Kruskal-Wallis检验确定NEDD8- cullin抑制组之间的统计学差异。为了分析肿瘤切片中CDT1和磷酸化CHK1(Ser317)水平,用相关抗体染色福尔马林固定,石蜡包埋的肿瘤切片,用HRP标记的二抗扩增并用ChromoMap DAB试剂盒检测。载玻片用苏木精复染。使用Eclipse E800显微镜和Retiga EXi彩色数码相机捕获图像并使用Metamorph软件处理。 CDT1和磷酸化CHK1水平表示为DAB信号区域的函数。大鼠[2]使用10周龄雄性Sprague-Dawley大鼠。在两项研究中,每组共8只动物给予载体,TNF-α,MLN4924或MLN4924 + TNF-α。首先静脉内给予动物载体(1×PBS)或10μg/ kg TNF-α。 1小时后,将它们皮下施用载体(20%磺基丁基醚β-环糊精在50mM柠檬酸盐缓冲液,pH3.3中)或120mg/kg MLN4924。预定的安乐死发生在给药后24小时。当动物表现出垂死的条件时,进行非计划的安乐死。在尸体剖检时收集血清,并由Idexx Laboratories分析肝损伤的血清化学标记物。此外,将每组5只动物的肝脏取出,分成两部分,在-80℃冷冻后进行蛋白质分析或固定在10%中性缓冲福尔马林中,石蜡包埋,切片4-6μm,安装在载玻片上,用苏木精和曙红染色,并用Olympus BX51光学显微镜进行组织病理学评估。根据用于对大鼠肝脏内的病变进行分类的标准化命名法记录显微镜检查结果。 |
Data Literature Source | [1]. Soucy TA,et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009 Apr 9;458(7239):732-6. [2]. F S Wolenski,et al. The NAE inhibitor pevonedistat (MLN4924) synergizes with TNF-α to activate apoptosis. Cell Death Discovery 1,Article number: 15034 (2015) |
Unit | Piece |
Specification | 5mg 10mM*1mL in DMSO |
MLN4924 是一种有效,选择性的NEDD8 活化酶 (NAE) 抑制剂。