2. Cell Cycle/DNA Damage Apoptosis
  3. DNA Alkylator/Crosslinker Topoisomerase Caspase Bcl-2 Family Apoptosis
  4. MN33-47

MN33-47 是一种 Bcl-2 抑制剂、caspase-3 激活剂和 DNA 交联剂，具有广谱抗癌活性。MN33-47 可提高 SN-38 (HY-13704) 的水溶性，并呈剂量依赖性抑制肿瘤生长和增殖，无明显毒性。MN33-47 可解除线粒体凋亡通路的抑制状态，启动凋亡 (apoptosis) 程序，抑制 Topo I 活性，并通过泛素-蛋白酶体和自噬-溶酶体通路促进其降解。MN33-47 诱导 DNA 交联、G2/M 期细胞周期阻滞、癌细胞迁移抑制，并通过线粒体通路诱导癌细胞凋亡。MN33-47 可用于结直肠腺癌、宫颈腺癌、肝细胞癌、肺泡基底上皮腺癌、胃癌及结肠癌的研究。

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MN33-47

MN33-47 Chemical Structure

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MN33-47 相关抗体

Top Publications Citing Use of Products

查看 Topoisomerase 亚型特异性产品:

查看所有亚型
Topoisomerase Topo I Topo II DNA gyrase

查看 Caspase 亚型特异性产品:

查看所有亚型
Caspase 1 Caspase 2 Caspase 3 Caspase 4 Caspase 5 Caspase 6 Caspase 7 Caspase 8 Caspase 9 Caspase 10 Caspase 12 Caspase Caspase 11 Caspase-13

查看 Bcl-2 Family 亚型特异性产品:

查看所有亚型
Bcl-2 Bcl-xL Bcl-W Mcl-1 Bfl-1 Bcl-B Bax Bak Bim BNIP3 Bad

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

MN33-47 is a multi-target anti-tumor compound with broad-spectrum anti-proliferative activity. MN33-47 relieves the inhibition of the mitochondrial apoptosis pathway by downregulating the anti-apoptotic protein Bcl-2, while activating caspase-3 and inhibiting Topoisomerase I activity, thereby promoting its degradation through the ubiquitin-proteasome and autophagy-lysosome pathways. MN33-47 can also induce DNA cross-linking and G2/M cell cycle arrest, inhibit cancer cell migration and activate the mitochondrial apoptosis pathway, thus exerting potent anti-tumor effects. MN33-47 can improve the water solubility of SN-38 (HY-13704), and exhibits dose-dependent tumor growth inhibition effects in CT26 tumor-bearing mouse models without obvious toxic and side effects. MN33-47 can be used in related studies on colorectal adenocarcinoma, cervical adenocarcinoma, hepatocellular carcinoma, alveolar basal epithelial adenocarcinoma, gastric cancer and colon cancer[1].

IC50 & Target

Topoisomerase I

 

Caspase 3

 

Bcl-2

 

体外研究
(In Vitro)

MN33-47 (0.038-100000 nM; 72 h) 可强效抑制 HCT-15、HeLa、HepG2、A549、HGC-27 和 CT26 细胞的增殖，IC50=4.77-252.10 nM，与对照处理相比，对 HeLa、HepG2 和 CT26 细胞的活性更强[1]。
MN33-47 (100 nM; 24, 48 h) 可在 24 h 和 48 h 时显著抑制 CT26 细胞的迁移，其疗效优于单药 chlormethine hydrochloride (HY-B1253) (CH) 或 SN-38 (HY-13704)[1]。
MN33-47 (100 nM; 48 h) 可在 48 h 后诱导 46.3% 的 CT26 细胞发生 G2/M 期阻滞，其细胞周期阻滞作用强于 CH、SN-38 或它们的物理混合物[1]。
MN33-47 (100 nM; 48 h) 可在 48 h 后诱导 50.63% 的 CT26 细胞发生凋亡，其促凋亡功效显著优于 CH、SN-38 或它们的物理混合物[1]。
MN33-47 (1-10000 nM, 1 μM; 72 h) 可通过泛素-蛋白酶体和自噬-溶酶体通路剂量依赖性降低 CT26 细胞中的 Topo I 蛋白水平；且在 1 μM 浓度下，其下调 Bcl-2 和激活 caspase-3 的效果优于 SN-38、CH 或二者的物理混合物[1]。

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

MN33-47 相关抗体:

Cell Proliferation Assay[1]

Cell Line: HCT-15, HeLa, HepG2, A549, HGC-27, CT26
Concentration: 0.038-100000 nM
Incubation Time: 72 h
Result: Exhibited broad-spectrum antiproliferative activity across all six cell lines, with IC50 values of 8.06 nM (HCT-15), 24.43 nM (HeLa), 6.24 nM (HepG2), 252.10 nM (A549), 34.55 nM (HGC-27), and 4.77 nM (CT26).
Showed superior potency to control groups including SN-38, CH, and their physical mixture in select cell lines, with significantly enhanced inhibition against HeLa, HepG2, and CT26 cells compared to MN33-45.

Cell Cycle Analysis[1]

Cell Line: CT26
Concentration: 100 nM
Incubation Time: 48 h
Result: Induced substantial G2/M phase arrest in CT26 cells, with 46.3% of cells in the G2/M phase, compared to 8.98% in the untreated control group.
Showed a significantly stronger arrest than that induced by CH, SN-38, or their physical mixture.

Apoptosis Analysis[1]

Cell Line: CT26
Concentration: 100 nM
Incubation Time: 48 h
Result: Induced an apoptosis rate of 50.63% in CT26 cells, which was significantly higher than the rates induced by CH (15.91%), SN-38 (25.00%), or their physical mixture (38.20%).

Western Blot Analysis[1]

Cell Line: CT26
Concentration: 1-10000 nM (72 h incubation); 1 μM (72 h incubation)
Incubation Time: 72 h
Result: Reduced Topo I protein levels in a dose-dependent manner, with the strongest inhibition observed at 10 μM.
At 1 μM, inhibited Topo I expression more effectively than SN-38, CH, or their physical mixture.
Downregulated Bcl-2 expression and reduced total caspase-3 protein levels (indicating activation of caspase-3) more strongly than control groups at 1 μM.
The reduction in Topo I levels induced by MN33-47 was reversed by the proteasome inhibitor MG132 and autophagy-lysosome inhibitor chloroquine.
体内研究
(In Vivo)

MN33-47 (1.56-6.24 mg/kg；腹腔注射；每日一次；连续 10 天) 在荷 CT26 肿瘤的 BALB/c 小鼠中展现出剂量依赖性的强效抗肿瘤活性，在 6.24 mg/kg 的高剂量下达到 75.73% 的肿瘤抑制率，且未观察到全身毒性或器官损伤[1]。

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

Animal Model: BALB/c mice with Colon cancer (female, 4-5 weeks old, 19-21 g, subcutaneous colon cancer xenograft)[1]
Dosage: 1.56 mg/kg; 3.12 mg/kg; 6.24 mg/kg
Administration: i.p.; daily; 10 days
Result: Achieved a tumor inhibition rate of 75.73% in the 6.24 mg/kg group.
Showed dose-dependent tumor growth inhibition.
Reduced tumor volume markedly in all dose groups compared to vehicle control, with the high-dose group having the smallest tumor mass.
Induced dose-dependent increases in tumor necrotic areas, reduced tumor cell density, and nuclear condensation, with the high-dose group showing the most pronounced effects.
Caused no significant body weight loss in any dose group.
Maintained serum ALT, AST, BUN, and CREA levels within normal reference ranges in all dose groups.
Showed no significant pathological alterations in heart, liver, spleen, lung, and kidney tissues in any dose group.
分子量

596.89

Formula

C27H28Cl3N3O6
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

MN33-47 相关分类

  • 摩尔计算器

  • 稀释计算器

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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:

MN33-47DNA Alkylator/CrosslinkerTopoisomeraseCaspaseBcl-2 FamilyApoptosisTopoisomerase IHCT-15colorectal adenocarcinomaHGC-27caspase-3HepG2HeLaA549CT26Bcl-2Inhibitorinhibitorinhibit

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