CAS:1028486-01-2
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:White to yellow Solid
是选择性的 Aurora A 抑制剂。
Array ( [133] => Array ( [id] => 133 [name] => Inhibitors & Antagonists & Agonists [num] => 3416 [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 ) ) ) )
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AliertibCAS:1028486-01-2
Storage:Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year
Purity:≥98%
Appearance:White to yellow Solid
CAS | 1028486-01-2 |
English Name | Aliertib |
Synonyms | 阿利色替;MLN8237 |
Molecular Formula | C27H20ClFN4O4 |
Molecular Weight | 518.92 |
Solubility | Soluble in DMSO |
Purity | ≥98% |
Appearance | White to yellow Solid |
Storage | Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
EC | EINECS 1592732-453-0 |
MDL | MFCD16621243 |
SMILES | O=C(C1=CC=C(C=C1OC)NC2=NC=C3CN=C(C4=CC(Cl)=CC=C4C3=N2)C5=C(C=CC=C5F)OC)O |
Target Point | Aurora Kinase |
Passage | Cell Cycle |
Background | Aliertib/mLN 8237 is a selective Aurora A inhibitor. |
Biological Activity | Alisertib 是选择性的 Aurora A 抑制剂,IC50为1.2 nM[1-4]。 |
IC50 | Aurora A:1.2nM [1-4] |
In Vitro | Alisertib引导MM细胞有丝分裂纺锤体异常,有丝分裂积累,以及通过细胞凋亡和衰老抑制细胞增殖。 Alisertib上调p53和肿瘤抑制基因p21和p27 [1]。 MLN8054/Alisertib对T217D/W277E Aurora A/TPX2复合物的活性降低可能反映了辅因子与Aurora A结合诱导的ATP亲和力增加[2]。 Alisertib抑制细胞增殖,在不同的tumer细胞系中IC50值范围为15至469 nM [3]。 |
In Vivo | Alisertib(20,30 mg/kg,po)在实体肿瘤异种移植模型中引起肿瘤生长抑制和淋巴瘤体内模型的消退,并降低HCT-116异种移植肿瘤中的FLT摄取[3]。Alisertib(30 mg/kg,po)显著降低肿瘤负荷并增加人类MM的异种移植物 - 鼠模型的总体存活率[1]。 |
Cell Experiment | 将MM细胞系与DMSO或Alisertib(0.125-0.5μM)一起与常规抗MM剂美法仑(2.5-5μM),多柔比星(50-100nM)或地塞米松(50-100nM)一起温育;并用新型抗MM剂硼替佐米(2.5-5nM)或来那度胺(0.5-1μM)72小时。通过MTT测定法测量细胞活力。组合指数(CI)通过使用CalcuSyn软件2.0版的等效线图分析确定(CI 1,没有显著的组合效应)。 |
Animal Experiment | 照射小鼠(200cGy),然后在右胁腹皮下接种5×106MM1.S细胞。当肿瘤生长可测量时(注射后2周),将小鼠分成4组(每组10只小鼠)口服载体(100μL10%2-羟丙基-β-环糊精/ 1%碳酸氢钠)或Alisertib(7.5)最终制剂中的mg/kg,15mg/kg和30mg/kg,在10%2-羟丙基-β-环糊精/ 1%碳酸氢钠中)连续21天。 Alisertib在大多数小鼠品系中的最大耐受剂量(连续给药21天)约为20mg/kg,每天两次(40mg/kg每天)。每隔一天通过游标卡尺测量肿瘤体积,并使用以下公式计算:长度×宽度2×0.5。在治疗结束时,最后一次治疗后2小时或肿瘤达到2 cm3时处死小鼠;立即从小鼠收集肿瘤,并通过TdT介导的dUTP缺口末端标记(TUNEL)测定评估诱导细胞凋亡和细胞死亡。 |
Kinase Experiment | 为了测量Aurora A活性,使用组蛋白H3作为底物,在适当的抑制剂(MLN8054,Alisertib)存在下测定25ng(12.5mM终浓度)或250ng(125nM终浓度)纯化的细菌表达的Aurora A.在100μM[γ-32P] ATP存在下,在30℃下20分钟。对于Aurora A/TPX2测定,包括50ng TPX2 [1-43]肽,其代表超过Aurora A的2倍摩尔过量。在随后添加抑制剂和ATP之前,Aurora A/TPX2复合物在激酶反应中进行。 |
Data Literature Source | [1]. Güllü G,et al. A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma Blood June 24,2010 vol. 115 no. 25 5202-5213 [2]. Sloane DA,et al. Drug-Resistant Aurora A Mutants for Cellular Target Validation of the Small Molecule Kinase Inhibitors MLN8054 and MLN8237 ACS Chem. Biol.,2010,5 (6),pp 563-576 [3]. Manfredi MG,et al. Characterization of Alisertib (MLN8237),an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays.Clin Cancer Res. 2011 Dec 15;17(24):7614-7624. [4]. Yayi Feng,et al. Targeting aurora a kinase (AURKA) and P21-activated kinase 1 (PAK1) in hormone receptor-positive breast cancer. College of Medicine. Drexel University. November 2016. |
Unit | Bottle |
Specification | 5mg 10mg |
是选择性的 Aurora A 抑制剂。