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

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.

For research use only. We do not sell to patients.

MN33-47

MN33-47 Chemical Structure

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Description

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

 

In Vitro

MN33-47 (0.038-100000 nM; 72 h) potently inhibits the proliferation of HCT-15, HeLa, HepG2, A549, HGC-27, and CT26 cells with IC50=4.77-252.10 nM, showing enhanced activity against HeLa, HepG2, and CT26 cells relative to control treatments[1].
MN33-47 (100 nM; 24, 48 h) significantly inhibits the migration of CT26 cells at 24 h and 48 h, showing greater efficacy than single-agent chlormethine hydrochloride (HY-B1253) (CH) or SN-38 (HY-13704)[1].
MN33-47 (100 nM; 48 h) induces G2/M phase arrest in 46.3% of CT26 cells after 48 h, showing stronger cell cycle blockade than CH, SN-38, or their physical mixture[1].
MN33-47 (100 nM; 48 h) induces apoptosis in 50.63% of CT26 cells after 48 h, exhibiting significantly greater pro-apoptotic efficacy than CH, SN-38, or their physical mixture[1].
MN33-47 (1-10000 nM, 1 μM; 72 h) dose-dependently reduces Topo I protein levels in CT26 cells via the ubiquitin-proteasome and autophagy-lysosome pathways, and at 1 μM, it more effectively downregulates Bcl-2 and activates caspase-3 than SN-38, CH, or their physical mixture[1].

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

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.
In Vivo

MN33-47 (1.56-6.24 mg/kg; i.p.; daily; 10 days) exhibits dose-dependent, potent antitumor activity in CT26 tumor-bearing BALB/c mice, achieving a 75.73% tumor inhibition rate at the high dose of 6.24 mg/kg, with no observable systemic toxicity or organ damage[1].

MedChemExpress (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.
Molecular Weight

596.89

Formula

C27H28Cl3N3O6

SMILES

CCC1=C2C(C(N3C2)=CC([C@@](O)(CC)C(OC4)=O)=C4C3=O)=NC5=CC=C(OC(N(CCCl)CCCl)=O)C=C51.Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
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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.

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Product Name:
MN33-47
Cat. No.:
HY-182759
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