5.05477

MLN4924

≥98% (HPLC), solid, NAE inhibitor, Calbiochem^®

• 同義詞: 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
• 經驗公式（希爾表示法）: C₂₁H₂₅N₅O₄S
• CAS號碼: 951950-33-7
• 分子量：: 443.52
• 分類程式碼代碼: 12352200
• NACRES: NA.77

屬性

• product name: NAE抑制剂，MLN4924,
• 化驗: ≥98% (HPLC)
• 品質等級: 100
• 形狀: solid
• 效力: 4.7 nM IC₅₀
• 製造商／商標名: Calbiochem^®
• 儲存條件: OK to freeze; protect from light
• 顏色: light beige
• 溶解度: DMSO: 100 mg/mL
• 儲存溫度: 2-8°C

描述

一般說明

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.

應用

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

包裝

用惰性气体包装

警告

毒性：标准处理（A）

重構

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。

其他說明

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.

法律資訊

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

安全資訊

• 儲存類別代碼: 11 - Combustible Solids
• 水污染物質分類（WGK）: WGK 2
• 閃點（°F）: Not applicable
• 閃點（°C）: Not applicable