product name
NAE抑制剂，MLN4924,
检测方案
≥98% (HPLC)
质量水平
形式
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 is a specific small molecule NEDD8-activating enzyme (NAE) inhibitor. Neddylation involves adding Nedd8, an ubiquitin-like molecule, to target proteins. This post-translational protein modification is associated with cancer development. MLN4924 is known to induce dose-dependent anti-proliferation, anti-migration, anti-invasion in ccRCC cells. MLN4924 is a cell-permeable AMP mimetic. The mechanism of action is found to target the NEDD8-activating E1 enzyme NAE nucleotide-binding site and undergoes a NAE-catalyzed covalent NEDD8 adduct formation, the adduct in turn acts as a tight-binding, ATP-competitive NAE inhibitor (IC50 = 4.7 nM), exhibiting much reduced or little potency against UAE/UBA1, UBA6/UBE1L2, SAE, ATG7, adenosine receptors A1/A2A/A2B/A3, or a panel of 12 cellular kinases. Selectively reduces cellular Ubc12-NEDD8, but not Ubc9-SUMO or Ubc10-Ub, thioester formation (ICmax = 90 nM in HCT-116 cultures in 24 h), resulting in cullin-RING ligases substrates elevation. Shown to inhibit the growth of various cancer cells both in cultures (IC50 from 50 nM to 1.03 µM) in vitro and in murine xenograft models (30 to 60 mg/kg via s.c.) in vivo via apoptosis induction.
应用
MLN4924 has been used as a neddylation inhibitor:
- to treat cell lines stably expressing a GaLV/MLV chimera construct in order to study its effects on viral transduction and infectivity
- to study its effects on the accumulation of LCMT1, suggesting a potential role in regulating LCMT1 stability and degradation in LNCaP cells
- to study UBX-390-mediated degradation of androgen receptor (AR) via proteasomal action in a prostate cancer cell line
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
警告
毒性：标准处理（A）
重悬
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
储存分类代码
11 - Combustible Solids
WGK
WGK 2
闪点(°F)
Not applicable
闪点(°C)
Not applicable
Shuai Tong et al.
Scientific reports, 7(1), 5599-5599 (2017-07-19)
Neddylation is a post-translational protein modification associated with cancer development. MLN4924 is a neddylation inhibitor currently under investigation in multiple phase I studies on various malignancies, and its clincal name is Pevonedistat. It has been documented that MLN4924 blocks Cullins
Soohyun Lee et al.
Advanced science (Weinheim, Baden-Wurttemberg, Germany), e2400398-e2400398 (2024-07-03)
The androgen receptor (AR) is an attractive target for treating prostate cancer, considering its role in the development and progression of localized and metastatic prostate cancer. The high global mortality burden of prostate cancer, despite medical treatments such as androgen
Carolyn A Robinson et al.
Viruses, 14(4) (2022-04-24)
HIV-1 Vpu targets the host cell proteins CD4 and BST-2/Tetherin for degradation, ultimately resulting in enhanced virus spread and host immune evasion. The discovery and characterization of small molecules that antagonize Vpu would further elucidate the contribution of Vpu to
Reyaz Ur Rasool et al.
Nature communications, 14(1), 5253-5253 (2023-08-30)
Loss of the tumor suppressive activity of the protein phosphatase 2A (PP2A) is associated with cancer, but the underlying molecular mechanisms are unclear. PP2A holoenzyme comprises a heterodimeric core, a scaffolding A subunit and a catalytic C subunit, and one
Rizwan Saffie et al.
Cancer research, 80(12), 2498-2511 (2020-05-01)
Mature B-cell neoplasms are the fifth most common neoplasm. Due to significant heterogeneity at the clinical and genetic levels, current therapies for these cancers fail to provide long-term cures. The clinical success of proteasome inhibition for the treatment of multiple
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