2. Autophagy PROTAC Apoptosis Metabolic Enzyme/Protease
  3. AUTACs Autophagy Glutathione Peroxidase Ferroptosis
  4. GPX4-AUTAC

GPX4-AUTAC 是一种靶向 GPX4 的自噬介导降解剂 (AUTAC)。GPX4-AUTAC 由抑制剂 ML162-yne (HY-153748)、降解标签 FBnG (HY-W073762) 和 glycol linker (HY-W021401) 组成。GPX4-AUTAC 能够促进 E3 连接酶 TRAF6 对 GPX4 的泛素化修饰，并增强其与 GPX4 和 p62 的结合，从而实现 GPX4 的选择性自噬依赖性降解。GPX4-AUTAC 显著诱导铁死亡 (ferroptosis)，并在乳腺癌细胞、乳腺癌来源的类器官 (PDOs) 和 MDA-MB-231 肿瘤异种移植小鼠模型中表现出强大的抗癌活性，与 Sulfasalazine (SAS) (HY-14655) 或化疗药物 (Paclitaxel (HY-B0015) 或 Cisplatin (HY-17394)) 联合使用时具有强效协同作用。

MCE 的所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务

GPX4-AUTAC Chemical Structure

GPX4-AUTAC Chemical Structure

1.  客户无需承担相应的运输费用。

2.  同一机构（单位）同一产品试用装仅限申领一次，同一机构（单位）一年内

     可免费申领三个不同产品的试用装。

3.  试用装只面向终端客户。

规格 是否有货
50 mg   询价  
100 mg   询价  
250 mg   询价  

* Please select Quantity before adding items.

Customer Review

GPX4-AUTAC 相关抗体

Top Publications Citing Use of Products

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

GPX4-AUTAC is a GPX4-targeting autophagy-mediated degrader (AUTAC). GPX4-AUTAC consists of an inhibitor ML162-yne (HY-153748), a degradation tag FBnG (HY-W073762) and a glycol linker (HY-W021401). GPX4-AUTAC promotes the ubiquitination of GPX4 by E3 ligase TRAF6, and enhances the binding with GPX4 and p62, leading to the selective autophagy-dependent degradation of GPX4. GPX4-AUTAC significantly induces ferroptosis and shows a potent anti-cancer activity in breast cancer cells, breast cancer-derived organoids (PDOs) and MDA-MB-231 tumor xenograft mice model, with potent synergistic effects when combined with Sulfasalazine (SAS) (HY-14655) or chemotherapy drugs (Paclitaxel (HY-B0015) or Cisplatin (HY-17394))[1].

体外研究
(In Vitro)

GPX4-AUTAC (5-80 μM，12-72 小时) 以剂量和时间依赖性方式显著降低 MDA-MB-231 和 MCF-7 细胞中 GPX4 的蛋白水平，但对 GPX4 的 mRNA 水平几乎没有影响[1]。
GPX4-AUTAC (20-40 μM，24 小时) 可有效降低卵巢癌、肺癌、黑色素瘤和胶质瘤细胞中 GPX4 的蛋白水平[1]。
GPX4-AUTAC (10 μM，24-96 小时，37-57℃) 持续下调 GPX4 蛋白水平长达 96 小时，并显著增强 MDA-MB-231 和 MCF-7 细胞中热变性的完整细胞和细胞裂解物中 GPX4 的热稳定性[1]。
GPX4-AUTAC (5-80 μM，24 小时) 选择性降解 GPX4，但不影响其他硒蛋白的表达，例如 GPX1、TXNRD1 (GPX4 同源物) 或 HK2 (TRAF6/p62 底物) [1]。
GPX4-AUTAC 选择性降解 GPX4 并诱导肿瘤细胞 (MDA-MB-231 细胞) 的铁死亡，而对正常细胞 (MCF-10A 细胞) 的影响极小[1]。
GPX4-AUTAC (10 μM，24 小时) 以自噬依赖的方式加速 HEK293T 细胞中 GPX4 降解，增加 GPX4 的多泛素化，特别是内源性和外源性 K63 连接泛素链。[1]。
GPX4-AUTAC (10-40 μM，12 小时) 可被 PYR-41、NH4Cl 和 3-MA 逆转，从而减少 MDA-MB-231 细胞中 GPX4 的下调[1]。
GPX4-AUTAC (24 小时) 可诱导 GPX4 和 p62 共定位，并增加 PDOs 中 GPX4 与 LC3B 或 LAMP2 的共定位[1]。
GPX4-AUTAC (40 μM，24 小时) 选择性靶向 GPX4，且铁死亡在 MDA-MB-231 细胞中显著富集[1]。
GPX4-AUTAC (5-40 μM，72 小时) 具有特异性的铁死亡诱导作用，显著增强 MDA-MB-231 细胞中脂质 ROS 并促进 Fe2+ 的积累，但仅在 MCF-7 细胞中被铁死亡抑制 Ferrostatin-1 (Fer-1) (HY-100579) 完全挽救[1]。
GPX4-AUTAC (5-80 μM) 可诱导 MDA-MB-231 细胞的铁死亡并伴随线粒体功能障碍 (形态异常、内容致密和嵴破坏) 以及 PTGS2 mRNA 水平显著升高[1]。
GPX4-AUTAC (5-40 μM，24-96 小时) 以剂量和时间依赖性的方式抑制 MDA-MB-231 和 MCF-7 细胞细胞活力和增殖，且对 GPX4 的敲低不敏感[1]。
GPX4-AUTAC (5-40 μM，4 天) 显著抑制 PDOs 生长，减少其直径和明视野，而 GPX4 高表达的 PDOs 增加对 GPX4-AUTAC 的敏感性[1]。
GPX4-AUTAC (10-20 μM，4 天) 可下调 GPX4 表达，并诱导高水平 4-HNE 的铁死亡，抑制低水平 Ki67 的 PDOs 中癌细胞增殖[1]。
GPX4-AUTAC 与 Sulfasalazine 联合使用相比于单独使用 Sulfasalazine 而言，可在 MDA-MB-231 和 MCF-7 细胞以及 PDOs 中诱导更显著的铁死亡并具有更强的抗癌作用[1]。
GPX4-AUTAC (10 μM，72 小时或 4 天) 可使 MDA-MB-231 和 HCC1806 细胞对化疗敏感，并与化疗药物 (Paclitaxel or Cisplatin) 联合使用可协同抑制细胞活力和增殖以及 PDOs 的生长[1]。

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

GPX4-AUTAC 相关抗体:

Cell Viability Assay[1]

Cell Line: MCF-7 cells
Concentration: 5, 10, 20, 40 μM
Incubation Time: 72 h after Fer-1, Z-VAD-FMK, Nec-1, Olaparib or VX765 1 h
Result: Had a specific ferroptosis inductive effect , only fully rescued by the ferroptosis inhibitor ferrostatin-1 (Fer-1), but not by the inhibitor of apoptosis (Z-VAD-FMK), necroptosis (Nec-1), parthanatos (Olaparib), or pyroptosis (VX765) in MCF-7 cells.

Cell Viability Assay[1]

Cell Line: MDA-MB-231 cells, MCF-7 cells
Concentration: MDA-MB-231 cells, MCF-7 cells (5, 10, 20, 40 μM), shNT, shGPX4 cells (10, 20, 40, 80 μM)
Incubation Time: 72 h
Result: Dose-dependently inhibited tumor cell viability in both MDA-MB-231, MCF-7 and shGPX4 cells.

Cell Proliferation Assay[1]

Cell Line: MDA-MB-231 cells, MCF-7 cells
Concentration: 5, 10 μM
Incubation Time: 24, 48, 72, 96 h
Result: Dose- and time-dependently inhibited tumor cell proliferation in both MDA-MB-231 and MCF-7 cells.

Western Blot Analysis[1]

Cell Line: MDA-MB-231 cells, MCF-7 cells, MCF-10A cells
Concentration: MDA-MB-231 cells, MCF-7 cells, MCF-10A cells (5, 10, 20, 40, 80 μM)
Incubation Time: 12, 24, 48, 72 h
Result: Significantly reduced the expression of GPX4 protein in a dose- and time-dependent manner.
Significantly reduced the expression of GPX4 in MDA-MB-231 cells with minimal effect on MCF-10A cells at 24 h.

Western Blot Analysis[1]

Cell Line: MDA-MB-231 cells, MCF-7 cells
Concentration: 10 μM
Incubation Time: 24, 48, 72, 96 h
Result: Continuously down-regulated GPX4 protein level for 96 h after wash-out in MDA-MB-231 and MCF-7 cells.
Significantly enhanced the thermal stability of GPX4 in heat-denatured intact cells and cell lysates in MDA-MB-231 and MCF-7 cells at 37-57℃ and 24 h.

Western Blot Analysis[1]

Cell Line: MDA-MB-231 cells, HEK293T cells
Concentration: 10, 40 μM
Incubation Time: 12 h
Result: Significantly accelerated the turnover rate of GPX4 in MDA-MB-231 cells when added CHX at 10 μM.
Down-regulated GPX4 expression, but this effect reversed by PYR-41 (an inhibitor of cell-permeable ubiquitin E1 enzyme) in MDA-MB-231 cells at 10 μM.
Enhanced the down-regulation of GPX4 promoted by overexpression of p62, but rescued by knockdown of p62 in HEK293T cells at 40 μM.

Real Time qPCR[1]

Cell Line: MDA-MB-231 cells, MCF-7 cells
Concentration: 5, 10, 20, 40, 80 μM
Incubation Time: 24 h
Result: Played a regulatory role at the post-translational level ,and barely affected the mRNA level of GPX4 in both MDA-MB-231 and MCF-7 cells.

Immunofluorescence[1]

Cell Line: MDA-MB-231 cells
Concentration: 5, 10, 20, 40 μM
Incubation Time: 72 h
Result: Significantly enhanced the lipid ROS and promoted accumulation of Fe<>sup2+ in MDA-MB-231 cells.
体内研究
(In Vivo)

GPX4-AUTAC (10-20 mg/kg，腹腔注射，每日一次，连续 10-12 天) 具有强效的抗癌活性，通过在 MDA-MB-231 肿瘤异种移植小鼠模型中优先积累并选择性降解肿瘤组织中的 GPX4 (对正常组织的影响较小)，显著减少肿瘤重量和体积、GPX4 蛋白水平和 Ki67 百分比，同时升高 4-HNE 水平，且对重要器官无明显毒性[1]。
GPX4-AUTAC (10-20 mg/kg 联用 Sulfasalazine 100 mg/kg，腹腔注射，每日一次，持续 10-12 天) 与 Sulfasalazine 协同作用，在 MDA-MB-231 肿瘤异种移植小鼠模型中通过诱导铁死亡发挥强大的肿瘤抑制活性，并且未发现可测量的毒性[1]。

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

Animal Model: Female BALB/c nude mice (4-6 weeks old) were injected subcutaneously into the right flank with MDA-MB-231 cells (5 × 106 cells/mouse) [1].
Dosage: 10, 20mg/kg
Administration: i.p., daily for 10-12 days when the tumor size reached 50-100 mm
Result: Selectively degraded GPX4 in tumors tissues, but not in the normal tissues including the heart, lung, liver, spleen, and kidney.
Significantly decreased tumor weights and volumes in MDA-MB-231 tumor xenograft mice model.
Markedly decreased the protein level of GPX4 in MDA-MB-231 tumor xenograft mice model.
Effectively decreased percentage of Ki67, but increased percentage of Ki67 4-HNE in MDA-MB-231 tumor xenograft mice model.
Animal Model: Female BALB/c nude mice (4-6 weeks old) were injected subcutaneously into the right flank with MDA-MB-231 cells (5 × 106 cells/mouse) [1].
Dosage: 10, 20mg/kg or Sulfasalazine 100 mg/kg
Administration: i.p., daily for 10-12 days when the tumor size reached 50-100 mm
Result: Had a synergistic inhibitory effect on tumor growth combined with SAS in MDA-MB-231 tumor xenograft mice model.
Significantly decreased expressions of GPX4 and Ki67 and increased expression of 4-HNE combined with SAS in MDA-MB-231 tumor xenograft mice model.
分子量

1124.10

Formula

C50H57Cl2FN12O9S2
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

GPX4-AUTAC 相关分类

  • 摩尔计算器

  • 稀释计算器

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

质量   浓度   体积   分子量 *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

浓度 (start) × 体积 (start) = 浓度 (final) × 体积 (final)
× = ×
C1   V1   C2   V2
Help & FAQs
  • 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:

GPX4-AUTACAUTACsAutophagyGlutathione PeroxidaseFerroptosisAutophagy-targeting chimerasAUTACGPX4AnticancerPDOsMDA-MB-231 cellsMCF-7 cellsHEK293T cellstumor xenograft mice modelInhibitorinhibitorinhibit

您最近查看的产品:

Your information is safe with us. * Required Fields.

   产品名称：

  

* 需求量：

* 客户姓名：

 

* Email：

* 电话：

 

* 公司或机构名称：

   留言给我们：

Bulk Inquiry

Inquiry Information

产品名称：
GPX4-AUTAC
目录号：
HY-176220
需求量：

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

   产品名称：

  

* Lot #：

* 客户姓名：

 

* Email：

   电话：

 

* 部门：

* 公司或机构名称：

 

   留言给我们：

Request for HNMR Report

We have received your request and will respond to you as soon as possible.

嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z