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NCOA4 - 9a

目录号 : GC26219

NCOA4 - 9a 是一种铁蛋白自噬抑制剂,能够抑制erastin诱导的铁死亡,EC50值为0.29μM。

NCOA4 - 9a Chemical Structure

Cas No.:2650557-72-3

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1mg
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Sample solution is provided at 25 µL, 10mM.

Description

NCOA4 - 9a is an inhibitor of ferritinophagy that inhibits erastin-induced ferroptosis, with an EC50 value of 0.29μM[1]. NCOA4 - 9a blocks ferroptosis by reducing the amount of bioavailable intracellular ferrous iron through disrupting the NCOA4–FTH1 protein–protein interaction[2]. NCOA4 - 9a is widely used to interfere with the ferritin autophagy process, reduce the release of iron ions, and delay the neuronal death in the rat hippocampus[3].

In vitro, NCOA4 - 9a treatment (0.5μM) for 36 hours significantly reversed the upregulation of lipid ROS levels in HCT-116 cells induced by sodium butyrate (NaB)[4]. 10μM NCOA4 - 9a treatment for 4 hours significantly increased the expression of FTH1 protein in the goat sperm model of cryopreservation and enhanced sperm survival[5]. NCOA4 - 9a treatment (0.5μM; 24h) reversed the cell death of human periodontal ligament cells (hPDLCs) significantly decreased under the stimulation of compressive force (CF) and IL-1β[6]. NCOA4 - 9a pretreatment for 2 hours (2.5μM) reduced the expression of the NP protein of PR8 H1N1 virus in A549 cells and inhibited the replication of PR8 H1N1 virus[7].

In vivo, NCOA4 - 9a treatment via daily intraperitoneal injection (10mg/kg) for 5 consecutive days significantly inhibited the growth of leukemia tumors in the murine patient-derived xenograft (PDX) models of acute myeloid leukemia (AML), without affecting the body weight of the mice[8].

References:
[1] Fang Y, Chen X, Tan Q, et al. Inhibiting ferroptosis through disrupting the NCOA4–FTH1 interaction: a new mechanism of action[J]. ACS central science, 2021, 7(6): 980-989.
[2] Larrue C, Mouche S, Angelino P, et al. Ferritinophagy Is a Druggable Vulnerability of Quiescent Leukemic Stem Cells[J]. Blood, 2023, 142: 407.
[3] Chen J, Yan L, Zhang Y, et al. Maternal exposure to nanopolystyrene induces neurotoxicity in offspring through P53-mediated ferritinophagy and ferroptosis in the rat hippocampus[J]. Journal of Nanobiotechnology, 2024, 22(1): 651.
[4] Liu L, Liu Y, Zhou X, et al. Sodium butyrate induces ferroptosis in colorectal cancer cells by promoting NCOA4-FTH1-mediated ferritinophagy[J]. International Immunopharmacology, 2025, 163: 115188.
[5] Hai E, Li B, Song Y, et al. Superoxide anion-induced ferritinophagy is involved in ferroptosis occurrence of cashmere goat sperm during cryopreservation[J]. Journal of Integrative Agriculture, 2025.
[6] Liu L, Li D, Zhou Z, et al. Inhibition of NCOA4/FTH1-mediated ferritinophagy attenuates ferroptosis in PDLCs and alleviates orthodontically induced inflammatory root resorption[J]. Progress in Orthodontics, 2025, 26(1): 43.
[7] Ouyang A, Chen T, Feng Y, et al. The hemagglutinin of influenza A virus induces ferroptosis to facilitate viral replication[J]. Advanced Science, 2024, 11(39): 2404365.
[8] Larrue C, Mouche S, Angelino P, et al. Targeting ferritinophagy impairs quiescent cancer stem cells in acute myeloid leukemia in vitro and in vivo models[J]. Science Translational Medicine, 2024, 16(757): eadk1731.

NCOA4 - 9a是一种铁蛋白自噬抑制剂,能够抑制erastin诱导的铁死亡,EC50值为0.29μM[1]。NCOA4 - 9a通过破坏NCOA4–FTH1蛋白-蛋白相互作用,减少细胞内生物可利用的二价铁含量,从而阻断铁死亡[2]。NCOA4 - 9a被广泛用于干扰铁蛋白自噬过程,减少铁离子释放,并延缓大鼠海马中的神经元死亡[3]

在体外,使用0.5μM的NCOA4 - 9a处理36小时,显著逆转了丁酸钠(NaB)诱导的HCT-116细胞中脂质ROS水平的上调[4]。10μM的NCOA4 - 9a处理4小时,显著提高了冷冻保存的山羊精子模型中FTH1蛋白的表达,并增强了精子存活率[5]。NCOA4 - 9a处理(0.5μM;24小时)逆转了在压缩力(CF)和IL-1β刺激下显著降低的人牙周膜细胞(hPDLCs)的细胞死亡[6]。NCOA4 - 9a预处理2小时(2.5μM)降低了PR8 H1N1病毒的NP蛋白在A549细胞中的表达,并抑制了PR8 H1N1病毒的复制[7]

在体内,每日腹腔注射NCOA4 - 9a(10mg/kg),连续5天,显著抑制了急性髓系白血病(AML)患者来源异种移植(PDX)小鼠模型中白血病肿瘤的生长,且未影响小鼠的体重[8]

实验参考方法

Cell experiment [1]:

Cell lines

Human periodontal ligament stem cells (hPDLCs)

Preparation Method

hPDLCs were seeded at a density of 1×105 cells per well in a 6-well plate and cultured until the cell confluence reached 80%. To apply compressive force to the hPDLCs, a layer of glass sheet was placed on the cells, and a container with metal balls containing heavy metals was used to adjust the compressive force by changing the number of metal balls. Additionally, at a compressive force of 2g/cm2, 20ng/ml of IL-1β was added to the hPDLCs for 24 hours, and NCOA4 - 9a (0.5µM) was used for treatment simultaneously. Then, cell viability was analyzed.

Reaction Conditions

0.5µM; 24h

Applications

NCOA4 - 9a treatment reversed the phenomenon that cell viability of hPDLCs significantly decreased under the stimulation of CF and IL-1β.
Animal experiment [2]:

Animal models

Male Sprague-Dawley (SD) rats

Preparation Method

Male Sprague-Dawley (SD) rats weighing 180-220g were housed individually under standard conditions of temperature and humidity, and a 12h light-dark cycle, with free access to food and water. Rats were anesthetized with intraperitoneal injection of phenobarbital (60mg/kg). The left common carotid artery and external carotid artery were separated and ligated through a median cervical incision, and the pterygofrontal artery was separated as well. An arterial clamp was placed in the proximal and distal carotid arteries, and a 4-0 monofilament nylon suture was inserted through the incision, to a depth of 17-20mm. The filament was withdrawn to restore blood flow (reperfusion) after 1.5h of middle cerebral artery occlusion (MCAO). All the SD rats subjected to MCAO were randomly divided into four groups (n=18 per group). Vehicle, Fer-1 (10mg/kg), or NCOA4 - 9a (10mg/kg) was administered by intraperitoneal injection 0.5h before and 2h after MCAO occlusion. All the sham-operated control rats were performed the same surgical procedure without insertion of a filament. Collect brain tissue for analysis.

Dosage form

10mg/kg for twice; i.p.

Applications

NCOA4 - 9a treatment alleviate cerebral ischemic injury in rats and reduce the levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE).

References:
[1] Liu L, Li D, Zhou Z, et al. Inhibition of NCOA4/FTH1-mediated ferritinophagy attenuates ferroptosis in PDLCs and alleviates orthodontically induced inflammatory root resorption[J]. Progress in Orthodontics, 2025, 26(1): 43.
[2] Fang Y, Chen X, Tan Q, et al. Inhibiting ferroptosis through disrupting the NCOA4–FTH1 interaction: a new mechanism of action[J]. ACS central science, 2021, 7(6): 980-989.

化学性质

Cas No. 2650557-72-3 SDF
分子式 C27H28FN5 分子量 441.54
溶解度 DMSO: 40mg/mL, Need ultrasonic; Insoluble in water 储存条件 Store at -20°C
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1 mM 2.2648 mL 11.324 mL 22.648 mL
5 mM 453 μL 2.2648 mL 4.5296 mL
10 mM 226.5 μL 1.1324 mL 2.2648 mL
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