2. Immunology/Inflammation NF-κB Metabolic Enzyme/Protease MAPK/ERK Pathway Cell Cycle/DNA Damage Apoptosis
  3. Reactive Oxygen Species (ROS) p38 MAPK JNK PERK Ferroptosis
  4. SB-T-101141

SB-T-101141 是一种新型紫杉烷类药物。SB-T-101141 可有效诱导非典型铁死亡 (ferroptosis)，从而克服乳腺癌对 Paclitaxel (HY-B0015) 的耐药性。SB-T-101141 促进铁离子、亚铁离子和活性氧 (ROS) 的产生。SB-T-101141 稳定地与 KHSRP 结合，抑制与铁稳态相关的铁依赖性 CISD1 表达。SB-T-101141 通过 KHSRP 协同增强铁依赖性的 JNK 和 PERK 通路激活。SB-T-101141 抑制 MCF-7(PR)/MDA-MB-231(PR) 或 KHSRP 敲除 MCF-7 异种移植小鼠模型中的乳腺肿瘤生长。

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SB-T-101141

SB-T-101141 Chemical Structure

CAS No. : 186348-05-0

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SB-T-101141 相关抗体

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  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

SB-T-101141 is a novel taxane. SB-T-101141 effectively induces a noncanonical ferroptosis to overcome Paclitaxel (HY-B0015) resistance of breast cancer. SB-T-101141 facilitates the production of iron and ferrous ions and ROS. SB-T-101141 stably binds to KHSRP to inhibit the iron-dependent expression of CISD1 related to iron homeostasis. SB-T-101141 synergistically enhances the iron-dependent activation of JNK and PERK pathways via KHSRP. SB-T-101141 suppresses breast tumor growth in MCF-7(PR)/MDA-MB-231(PR) or KHSRP knock-down MCF-7 xenograft mice model[1].

体外研究
(In Vitro)

SB-T-101141 (1-3 μM，12 小时) 可有效诱导 MCF-7 和 MDA-MB-453 细胞中的微管聚合和微管蛋白表达[1]。
SB-T-101141 (1-3 μM，72 小时) 具有强效细胞毒性，对 MCF-7、MDA-MB-453 和 MDA-MB-231 细胞的 IC50 分别为 0.03、0.8 和 6.5 μM，而对正常 MCF-10A 细胞的作用相似[1]。
SB-T-101141 (0.001-8 μM，1-14 天) 可强烈抑制 MCF-7 和 MDA-MB-453 细胞的增殖和集落形成，并增加细胞死亡细胞[1]。
SB-T-101141 (9 μM，5 天）可有效抑制患者乳腺癌类器官的生长[1]。
SB-T-101141 (1-8 μM，12-60 小时) 在 1 μM 浓度下显著诱导 MCF-7 和 MDA-MB-453 细胞中细胞凋亡和 G2/M 期阻滞(高剂量时无效)，且不改变裂解的 PARP 和 caspase-7 的水平[1]。
SB-T-101141 (3-16 μM，4-72 小时) 诱导MCF-7 和 MDA-MB-453 细胞呈现铁死亡样死亡形态，且在细胞内蓄积较少，并使膜通透性增加，而这种效应可被 Z-VAD-FMK 和 Necrostatin-1 显著阻断，但只对的线粒体数量和 ATP 水平有轻微影响[1]。
SB-T-101141 (0.17-8 μM，0-48 小时) 显著增加 MCF-7、MDA-MB-453 和 MCF-7PR 细胞中铁和亚铁离子以及 MDA 水平，降低 GSH 水平，而对 GPX4 表达没有明显影响[1]。
SB-T-101141 (0.17-16 μM，3-48 小时）诱导 MCF-7、MDA-MB-453、MCF-7PR 和 MDA-MB-453PR 细胞中总 ROS (被 DFOM 和 NAC 中和)、脂质 ROS 和膜通透性，导致细胞活力受损和细胞死亡，而 DFOM、Fer-1 或 Lip-1 无法减弱这种效应。[1]。
SB-T-101141 (3-5 nM，14 天) 显著抑制 Paclitaxel 耐药的 MCF-7PR 和 MDA-MB-231PR 细胞增殖[1]。
SB-T-101141 (0.25-1.5 μM，24 小时) 诱导 MCF-7PR 和 MDA-MB-453PR 细胞中 Paclitaxel 耐药细胞死亡，并且这种效应仅被铁螯合剂 DFOM 和 CPX 有效抑制[1]。
SB-T-101141 (0.001-3 μM，1-14 天) 对敲低 KHSRP 的 MCF-7 细胞比敲低 HDGF 和 CYP2S1 的细胞更敏感[1]。
SB-T-101141 (0.01-100 μM，2-24 小时) 可增强 KHSRP 蛋白的热稳定性，但不影响 MCF-7 细胞中 KHSRP 的表达[1]。
SB-T-101141 (1.5-3 μM，0-24 小时) 通过KHSRP 促进 MCF-7 和 MCF-7PR 细胞中脂质过氧化，并有效降低 CISD1 的 mRNA 和蛋白质水平[1]。
SB-T-101141 (10 μM，4 小时) 显著影响内质网应激相关的 G3BP1 颗粒聚集，但不影响 G3BP1 的表达[1]。
SB-T-101141 (0.17-16 μM，24-48 小时) 可提高 MCF-7、MDA-MB-453、MCF-7PR 和 MDA-MB-231PR 细胞中 eIF2α 的蛋白水平，并通过铁依赖性的 JNK 和 PERK 信号传导诱导细胞死亡[1]。

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

SB-T-101141 相关抗体:

Cell Viability Assay[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 3  μM (MCF-7 cells), 8  μM (MDA-MB-453 cells)
Incubation Time: 12, 24, 36, 48, 60, 72 h
Result: Efficiently increased cell death in MCF-7 and MDA-MB-453 cells.
Induced cell death but this effect was reversed by apoptosis inhibitor (Z-VAD-FMK) (HY-16658B) and necrosis inhibitor (Necrostatin-1) (HY-15760).
Significantly increased Paclitaxel-resistant MCF-7PR and MDA-MB-231PR cells survival with IC50 of 2.7 and 0.235 μM, respectively.

Immunofluorescence[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 1 μM
Incubation Time: 12 h
Result: Efficiently induced microtubule polymerization.

Western Blot Analysis[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 1,3 5 μM (MCF-7 cells), 8 μM (MDA-MB-453 cells)
Incubation Time: 12, 24, 36, 48, 60 h
Result: Significantly increased the tubulin protein expression in MCF-7 cells at 12 h.
Induced no cleavages of PARP and caspase-7 protein expression changes during 12-60 h in MCF-7 and MDA-MB-453 cells.

Cell Proliferation Assay[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 1 nM, 2  μM (MCF-7 cells), 1 nM, 5  μM (MDA-MB-453 cells)
Incubation Time: 1, 14 days
Result: Significantly decreased cell proliferation at 1 day in MCF-7 and MDA-MB-453 cells.
Strongly inhibited colony formation at 1 nM after 14 days in MCF-7 and MDA-MB-453 cells.

Apoptosis Analysis[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 1 μM
Incubation Time: 48 h
Result: Significantly induced cell apoptosis with late apoptosis population from 7.38% to 17.81% in MCF-7 cells and MDA-MB-453 cells (10.51% to 30.76%).

Cell Cycle Analysis[1]

Cell Line: MCF-7 cells, MDA-MB-453 cells
Concentration: 1,3 μM (MCF-7 cells), 1,8 μM (MDA-MB-453 cells)
Incubation Time: 24 h
Result: Significantly induced G2/M phase arrest with G2/M phase population from 11.67% and 9.26% to 23.02% and 28.37% at 1 μM in MCF-7 and MDA-MB-453 cells, respectively.
Induced no G2/M phase arrest at high dose of 3 and 8 μM in MCF-7 and MDA-MB-453 cells, respectively.
体内研究
(In Vivo)

SB-T-101141 (5 mg/kg，腹腔注射，每三天一次) 在 MCF-7(PR)/ MDA-MB-453(PR) 异种移植肿瘤小鼠模型中强烈抑制肿瘤生长，且对体重无副作用。[1]。
SB-T-101141 (5 mg/kg，腹腔注射，每三天一次) 在 KHSRP 基因敲低的 MCF-7 异种移植小鼠模型中，未诱导肿瘤生长抑制活性，且未增加醛 4-HNE 表达水平[1]。

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

Animal Model: Female immune-deficient BALB/c nude mice (4 weeks old) were injected subcutaneously with Estradiol cypionate (HY-B1100) following with MCF-7 cells (5 × 106 cells/mouse) or MDA-MB-453 cells (1 × 107 cells/mouse)[1].
Dosage: 5 mg/kg, Estradiol cypionate (1.5 mg/kg)
Administration: i.p., once every three days (Estradiol cypionate, once every seven days) and then measured body weight and tumor volume.
Result: Strongly repressed tumor growth in MCF-7/ MDA-MB-453 xenografted tumor mice model.
Caused no significant mouse body weight changes in MDA-MB-453 xenografted tumor mice model.
Had a strong antitumor effect on the Paclitaxel-resistant cell xenografted tumor progression without side effects on body weight.
Animal Model: Female immune-deficient BALB/c nude mice (4 weeks old) were injected subcutaneously with Estradiol cypionate following with KHSRP knock-down MCF-7 cells (6 × 106 cells/mouse)[1].
Dosage: 5 mg/kg, Estradiol cypionate (1.5 mg/kg)
Administration: i.p., once every three days (Estradiol cypionate, once every seven days) and then measured body weight and tumor volume.
Result: Induced no inhibitory activity in tumor growth without increase of lipid peroxidation product, aldehyde 4-HNE in KHSRP knock-down MCF-7 xenografted mice model
分子量

869.90

Formula

C44H55NO17
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

SB-T-101141 相关分类

  • 摩尔计算器

  • 稀释计算器

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  • Do most proteins show cross-species activity?

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Keywords:

SB-T-101141186348-05-0Reactive Oxygen Species (ROS)p38 MAPKJNKPERKFerroptosisc-Jun N-terminal kinaseProtein kinase R-like endoplasmic reticulum kinasePKR-like endoplasmic reticulum kinaseTaxaneAnticancerMCF-7(PR)/MDA-MB-231(PR) xenograft mice modelMCF-7PR cellsMDA-MB-231PR cellsInhibitorinhibitorinhibit

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