5.05477
MLN4924
≥98% (HPLC), solid, NAE inhibitor, Calbiochem®
别名:
NAE抑制剂，MLN4924, ((1S,2S,4R)-4-(4-((1S)-2,3-二氢-1H-茚满-1-基氨基)-7H-吡咯并[2,3-d]嘧啶-7-基} -2-羟基环戊基)氨基磺酸甲酯,NEDD8活化酶抑制剂
产品名称
NAE抑制剂，MLN4924,
方案
≥98% (HPLC)
质量水平
表单
solid
效能
4.7 nM IC50
制造商/商品名称
Calbiochem®
储存条件
OK to freeze
protect from light
颜色
light beige
溶解性
DMSO: 100 mg/mL
储存温度
2-8°C
一般描述
MLN4924 是一种特定的小分子 NEDD8 活化酶 (NAE) 抑制剂。Neddylation 涉及将泛素样分子 Nedd8 添加到靶蛋白中。这种翻译后蛋白质修饰与癌症发展有关。MLN4924确知可在 ccRCC 细胞中诱导剂量依赖性抗增殖、抗迁移、抗侵袭。MLN4924 是一种可穿透细胞的 AMP 模拟物。经证其作用机制可靶向NEDD8活化E1酶NAE核苷酸结合位点，并经历NAE催化的共价NEDD8加合物形成的细胞渗透性AMP模拟物，而该加合物反过来会作为一种紧密集合、ATP竞争性NAE抑制剂（IC50 = 4.7 nM），针对UAE/UBA1、UBA6/UBE1L2、SAE、ATG7、腺苷受体A1/A2A/A2B/A3或一组12种的细胞激酶表现了大幅减低或很低的效力。选择性降低细胞内Ubc12-NEDD8而非Ubc9-SUMO或Ubc10-Ub硫酯的形成（24小时内HCT-116培养物中的ICmax = 90 nM），从而导致cullin-RING连接酶底物升高。在体外（IC50从50 nM到1.03 µM）和体内鼠异种移植模型（30至60 mg/kg，通过s.c.）中均显示出可通过凋亡诱导而对各种癌细胞的生长进行抑制。
应用
MLN4924可用作 Neddylation 抑制剂：
- 处理稳定表达 GaLV/MLV 嵌合体构建体的细胞系，以研究其对病毒转导和传染性的影响
- 研究其对 LCMT1 积累的影响，揭示其在调节 LNCaP 细胞中 LCMT1 稳定性和降解方面的潜在作用
- 研究 UBX-390 通过蛋白酶体作用在前列腺癌细胞系中介导的雄激素受体 (AR) 降解
生化/生理作用
可逆：否
细胞可渗透性：具有
首要靶标
NEDD8活化酶
NEDD8活化酶
包装
用惰性气体包装
制备说明
仅使用新鲜的DMSO进行溶解。
溶解后，等分并冷冻保存（-20°C）。储备液可在-20°C最长稳定1个月。
其他说明
Milhollen, M.A., et al. 2010.Blood116, 1515.
Brownell, J.E., et al. 2010.Mol.Cell37, 102.
Soucy, T.A., et al. 2009.Nature458, 73.
Brownell, J.E., et al. 2010.Mol.Cell37, 102.
Soucy, T.A., et al. 2009.Nature458, 73.
法律信息
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
免责声明
毒性：标准处理（A）
储存分类代码
11 - Combustible Solids
WGK
WGK 2
闪点(°F)
Not applicable
闪点(°C)
Not applicable
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