2. Cell Cycle/DNA Damage Apoptosis Immunology/Inflammation NF-κB Metabolic Enzyme/Protease Autophagy
  3. Deubiquitinase Ferroptosis Reactive Oxygen Species (ROS) Glutathione Peroxidase Autophagy
  4. NCI677397

NCI677397 是一种 USP24 抑制剂。NCI677397 增加脂质 ROS，激活胆固醇和脂肪酸生物合成，通过自噬 (autophagy) 途径降解 ABC 转运蛋白、GPX4 和 DHFR，降低 p-gp 水平，最终导致耐药性癌细胞发生铁死亡 (ferroptosis)。NCI677397 可用于肺癌和脑癌的研究。

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NCI677397 Chemical Structure

NCI677397 Chemical Structure

CAS No. : 907547-06-2

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NCI677397 相关抗体

Top Publications Citing Use of Products

查看 Deubiquitinase 亚型特异性产品:

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USP1 USP2 USP7 USP8 USP10 USP30 UCHL1

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

NCI677397 is a USP24 inhibitor. NCI677397 increases lipid ROS, activates cholesterol and fatty acid biosynthesis, degrades ABC transporters, GPX4 and DHFR through the autophagy pathway, decreases the level of P-gp and ultimately leads to ferroptosis in drug-resistant cancer cells. NCI677397 can be used for the study of lung caner and brain cancer[1][2].

体外研究
(In Vitro)

NCI677397 (0-120 nM, 24 h-7 d) 能有效逆转多种癌症的耐药性：对紫杉醇 (Taxol) 耐药的肺癌 T24 细胞、对替莫唑胺 (TMZ) (HY-17364) 耐药的脑癌 Pt3-TMZR 和 U87-R 细胞、对喜树碱 (CPT) (HY-16560) 耐药的鼻咽癌 Hone-1-CPTR 细胞和对奥沙利铂 (oxaliplatin) (HY-17371) 耐药的结直肠癌 HCT116-OXR 细胞。 NCI677397 (10 and 20 μM, 4 天) 显著降低了对 TMZ 敏感和耐药的胶质母细胞瘤细胞的活力，并且与 TMZ 联合使用时具有协同作用[1]。
NCI677397 (0-20 μM, 24 h) 在对 TMZ 敏感和耐药的胶质母细胞瘤细胞和 A549 和紫杉醇耐药 A549 (A549-T24) 细胞中均能诱导自噬，而不能诱导细胞凋亡[1]。
NCI677397 (0-15 μM, 24 h) 能诱导 Pt’3、Pt’3R、U87、U87R、A549 和 A549-T24 细胞中胆固醇和脂肪酸的生物合成[1]。
NCI677397 (0-25 μM, 24 h) 通过脂质活性氧介导，诱导 U87、U87R、Pt'3、Pt'3R 和 A549-T24 细胞发生铁死亡[1]。
NCI677397 (0-25 μM, 24 h) 通过自噬途径降解 ABCG1/5/8，并降低 Pt'3R 和 A549-T24 细胞中 GPX4 和 DHFR 的稳定性[1]。
NCI677397 (20 μM, 0-24 h) 在 Pt'3R 细胞中 2 小时内诱导脂质过氧化，6 小时后上调胆固醇合酶，24 小时后完成铁死亡进程[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

NCI677397 相关抗体:

Cell Viability Assay[1]

Cell Line: TMZ-sensitive GBM cells (Pt’3, A172 and U87 cells) and TMZ-resistant GBM cells (Pt’3R, A172R and U87R cells)
Concentration: 0, 10 and 20 μM
Incubation Time: 4 days
Result: Significantly decreased the viability combined with TMZ treatment.

Western Blot Analysis[1]

Cell Line: TMZ-sensitive GBM cells (Pt’3, A172 and U87 cells) and TMZ-resistant GBM cells (Pt’3R, A172R and U87R cells)
Concentration: 0, 5, 10, 15, 20 μM
Incubation Time: 24 h
Result: Increased the levels of autophagosome-associated lipidated form of LC3B (LC3B-II).
Did not increase the levels of Bax, an apoptotic marker.
Increasing autophagic and apoptotic cell death with TMZ.

Immunofluorescence[1]

Cell Line: Pt’3R cells
Concentration: 15 μM
Incubation Time: 24 h
Result: Induced accumulation of LC3B spots.

Western Blot Analysis[1]

Cell Line: Pt’3, Pt’3R and A549-T24cells
Concentration: 0, 5, 10, 15, 20, 25 μM
Incubation Time: 24 h
Result: Increased the levels of p-IRE1a, Bip, XBP1, p-eIF2a and CHOP in Pt’3 cells.
Increased the levels of ACSL3 and ACSL4 in brain and lung cancer cells.
Increased heme oxygenase-1 (HO-1) and p62/SQSTM1.
Induced SLC47A1 upregulation in both A549-T24 and Pt30R cells.
体内研究
(In Vivo)

NCI677397Z (20 mg/kg, i.p., 1 周给药 2 次，共 7 周) 在 U87R 异种移植小鼠模型中显著抑制了肿瘤生长[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: U87R xenograft model established in male nonobese diabetic/severe combined immunodeficiency mice (8 weeks old)[1]
Dosage: 20 mg/kg
Administration: Intraperitoneal injection (i.p.), twice a week for 7 weeks
Result: led to smaller tumor size and lower tumor weight.
分子量

457.63

Formula

C28H31N3OS
CAS 号
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
纯度 & 产品资料
参考文献

NCI677397 相关分类

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

NCI677397907547-06-2NCI 677397NCI-677397DeubiquitinaseFerroptosisReactive Oxygen Species (ROS)Glutathione PeroxidaseAutophagyDUBsCancerLipid peroxidationSmall molecular inhibitorUSP24Inhibitorinhibitorinhibit

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