MG-002
MG-002 is an orally active eIF4A1 and eIF4A2 inhibitor with a human eIF4A1 IC50 of 43 nM. MG-002 prevents competent ribosome recruitment to mRNA, inhibits cap-dependent mRNA translation, and engages eIF4A2 via the same RNA clamping mechanism to inhibit mRNA translation. MG-002 induces G2/M cell cycle delay, induces apoptosis, suppresses synthesis of c-MYC and cyclin D1, and shows minimal overt toxicity in mice. MG-002 inhibits primary triple-negative breast cancer tumor growth, attenuates metastatic spread, and enhances anti-neoplastic activity of Doxorubicin (HY-15142A) in pre-clinical models.
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- No. CAS: 3076503-34-6
- Fòrmula: C27H25N3O7
- Peso molecular:503.50
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Actividad biológica
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eIF4A 43 nM (IC50) |
Cdk4/cyclin D1 |
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Cell Line
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Type | Value | Description | References |
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| 4T1 | EC50 |
1-10 nM
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Reduction of cell viability in 4T1 TNBC cells assessed via SRB staining after 2 d incubation.
Reduction of cell viability in 4T1 TNBC cells assessed via SRB staining after 2 d incubation.
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38232291 |
| BT-474 | EC50 |
1-10 nM
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Reduction of cell viability in BT474 ER+/HER2+ cells assessed via SRB staining after 4 d incubation.
Reduction of cell viability in BT474 ER+/HER2+ cells assessed via SRB staining after 4 d incubation.
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38232291 |
| MDA-MB-231 | EC50 |
1-10 nM
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Reduction of cell viability in MDA-MB-231 TNBC cells assessed via SRB staining after 2 d incubation.
Reduction of cell viability in MDA-MB-231 TNBC cells assessed via SRB staining after 2 d incubation.
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38232291 |
| 4T1 | IC50 |
7 nM
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Inhibition of mRNA translation in 4T1-526 TNBC cells assessed via puromycin incorporation.
Inhibition of mRNA translation in 4T1-526 TNBC cells assessed via puromycin incorporation.
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38232291 |
MG-002 (10 μM; 30 min) stabilizes eIF4A1 binding to polypurine poly(AG)8 RNA with a longer complex half-life than eFT226[1].
MG-002 (15 μM) stabilizes recombinant eIF4A1 protein structure via RNA clamping, as shown by a 7.2 °C ΔT50 shift in DSF analysis[1].
MG-002 (0.1-1000 nM; 1 h) potently inhibits cap-dependent mRNA translation in Krebs-2 extracts with an IC50 of 43 nM, while sparing eIF4A-independent HCV IRES-driven translation[1].
MG-002 (1-1000 nM; 1 h) potently inhibits protein synthesis in eHAP1 haploid leukemia cells after 1 h of exposure[1].
MG-002 (0.01-100 nM, 3 μM; 2-4 d) potently reduces viability of 4T1, BT474, and MDA-MB-231 breast cancer cells with EC50 values of ~1 to 10 nM, while exerting only modest cytostatic effects on non-transformed IMR-90, MRC-5, and HUVEC cells[1].
MG-002 (0.1-10000 nM; 2 d) exerts its cytotoxic effects primarily through engagement of eIF4A1 and eIF4A2[1].
MG-002 (7 nM; 72 h) inhibits mRNA translation in 4T1-526 TNBC cells with an IC50 of ~7 nM and induces significant cell death after 72 h of exposure to this concentration[1].
MG-002 (10 nM) induces a significant G2/M progression delay in MDA-MB-231 TNBC cells post-release from S phase block[1].
MG-002 (100 nM; 24 h) reduces eIF4F-sensitive c-MYC and cyclin D1 protein levels in MDA-MB-231, 4T1, and MRC-5 cells, and induces apoptosis (PARP cleavage) in MDA-MB-231 and 4T1 cancer cells but not in non-transformed MRC-5 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:4T1 TNBC, BT474 ER+/HER2+, MDA-MB-231 TNBC, IMR-90, MRC-5, HUVEC
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Concentration:0.01, 1, 10, 100 nM (breast cancer and non-transformed cells); 3 μM (non-transformed cells)
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Incubation Time:2 d (4T1, MDA-MB-231, non-transformed cells); 4 d (BT474)
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Result:Compromised viability in all breast cancer cell lines with EC50 values ranging from approximately 1 to 10 nM.
Exerted only a modest cytostatic effect in non-transformed IMR-90, MRC-5, and HUVEC cells, with viable cells never falling below 50% even at 3 μM.
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Cell Line:MDA-MB-231, 4T1, MRC-5 cells
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Concentration:100 nM
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Incubation Time:24 h
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Result:Reduced c-MYC and cyclin D1 protein levels in MDA-MB-231, 4T1, and MRC-5 cells.
Induced PARP cleavage, a marker of apoptosis, in MDA-MB-231 and 4T1 cancer cells, while no PARP cleavage was observed in non-transformed MRC-5 cells.
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Cell Line:eHAP1 cells, eIF4A1F163L/eIF4A2- eHAP1 cells, engineered eHAP1 derivative cell lines
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Concentration:0.1, 1, 10, 100, 1000, 10000 nM
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Incubation Time:2 d
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Result:Exhibited weaker potency against eIF4A1F163L/eIF4A2⁻ eHAP1 cells compared with parental eHAP1 cells.
Regained effective activity in eIF4A1F163L/eIF4A2⁻ cells upon exogenous overexpression of wild-type eIF4A1 or eIF4A2.
Failed to recover cellular sensitivity following ectopic expression of DDX3X, eIF4A3 or mutant eIF4A1F163L.
MG-002 (0.5 mg/kg; p.o.; every 3 days) enhances the anti-tumor efficacy of Doxorubicin (HY-15142A) in BALB/c mice with primary TNBC, significantly reducing tumor growth via increased apoptosis[1].
MG-002 (0.5 mg/kg; p.o.; every 3 days; until surgical resection) prevents the formation of spontaneous TNBC lung metastases in BALB/c mice[1].
MG-002 (0.5 mg/kg; p.o.; every 3 days for 21 days) modestly reduces established TNBC lung metastasis burden in BALB/c mice[1].
MG-002 (0.5 mg/kg; p.o.; every 3 days) enhances the anti-metastatic efficacy of Doxorubicin in BALB/c mice with established TNBC lung metastases[1].
MG-002 (0.5 mg/kg; i.p.; every 2 days) inhibits growth of human MDA-MB-231 TNBC tumors in SCID-beige mice when administered intraperitoneally[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c (female, 6 to 8 weeks old, triple-negative breast cancer model via 4T1-526 TNBC cells injected into mammary fat pads)[1]
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Dosage:0.5 mg/kg
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Administration:p.o.; every 3 days
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Result:Significantly reduced primary tumor growth compared to vehicle and eFT226 controls.
Reduced % Ki67-positive cells, indicating decreased tumor cell proliferation.
Increased % cleaved Caspase-3-positive cells.
Significantly reduced Myc protein levels in tumor tissue.
Caused no adverse effects on total body weight or liver weight.
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Animal Model:BALB/c (female, 6 to 8 weeks old, triple-negative breast cancer spontaneous lung metastasis model via 4T1-526 TNBC cells injected into mammary fat pads followed by surgical tumor resection)[1]
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Dosage:0.5 mg/kg
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Administration:p.o.; every 3 days; until surgical resection
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Result:Significantly reduced the area of spontaneous lung metastases compared to vehicle control.
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Animal Model:BALB/c (female, 6 to 8 weeks old, triple-negative breast cancer established lung metastasis model via 4T1-526 TNBC cells injected into tail vein)[1]
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Dosage:0.5 mg/kg
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Administration:p.o.; every 3 days; 21 days
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Result:Associated with a modest reduction in established lung tumor burden compared to vehicle control.
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Animal Model:BALB/c (female, 6 to 8 weeks old, triple-negative breast cancer model via 4T1-526 TNBC cells injected into mammary fat pads, combination regimen)[1]
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Dosage:0.5 mg/kg
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Administration:p.o.; every 3 days
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Result:Significantly reduced primary tumor growth when combined with doxorubicin compared to both monotherapies and vehicle control.
Increased tumor apoptosis when used alone, with a more pronounced increase observed with combination therapy.
Showed no significant difference in cell proliferation between treatments.
Caused no significant weight loss in mice with combination therapy.
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Animal Model:BALB/c (female, 6 to 8 weeks old, triple-negative breast cancer established lung metastasis model via 4T1-526 TNBC cells injected into tail vein, combination regimen)[1]
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Dosage:0.5 mg/kg
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Administration:p.o.; every 3 days
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Result:Significantly reduced established lung tumor burden when combined with doxorubicin compared to both monotherapies and vehicle control.
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Animal Model:SCID-beige (female, 6 to 8 weeks old, triple-negative breast cancer model via MDA-MB-231 TNBC cells injected into mammary fat pads)[1]
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Dosage:0.5 mg/kg
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Administration:i.p.; every 2 days
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Result:Delayed growth of MDA-MB-231 tumors.
Chemical Information
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No. CAS 3076503-34-6
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Peso molecular 503.50
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Fòrmula C27H25N3O7
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SMILES
O[C@]12[C@](OC3=CC(OC)=NC(OC)=C32)(C4=CC=C(C=C4)C#N)[C@H](C5=CC=CC=C5)[C@H]([C@H]1O)C(NOC)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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