Art. -Nr.: HY-173172

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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CAS. Nr.: 3076503-34-6
Formel: C₂₇H₂₅N₃O₇
Molecular Weight:503.50

Speicherung:

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

Data Sheet (294 KB)

MG-002 Chemical Structure

CAS. Nr.: 3076503-34-6

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target^[1]

eIF4A

43 nM (IC₅₀)

Cdk4/cyclin D1

Alle CDK Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
4T1	EC50	1-10 nM	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.	38232291
BT-474	EC50	1-10 nM	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.	38232291
MDA-MB-231	EC50	1-10 nM	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.	38232291
4T1	IC50	7 nM	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.	38232291

In Vitro

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.

Cell Viability Assay^[1]

Cell Line:

4T1 TNBC, BT474 ER+/HER2+, MDA-MB-231 TNBC, IMR-90, MRC-5, HUVEC
Concentration:

0.01, 1, 10, 100 nM (breast cancer and non-transformed cells); 3 μM (non-transformed cells)
Incubation Time:

2 d (4T1, MDA-MB-231, non-transformed cells); 4 d (BT474)
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.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231, 4T1, MRC-5 cells
Concentration:

100 nM
Incubation Time:

24 h
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.

Cell Viability Assay^[1]

Cell Line:

eHAP1 cells, eIF4A1F163L/eIF4A2^- eHAP1 cells, engineered eHAP1 derivative cell lines
Concentration:

0.1, 1, 10, 100, 1000, 10000 nM
Incubation Time:

2 d
Result:

Exhibited weaker potency against eIF4A1^F163L/eIF4A2⁻ eHAP1 cells compared with parental eHAP1 cells.
Regained effective activity in eIF4A1^F163L/eIF4A2⁻ cells upon exogenous overexpression of wild-type eIF4A1 or eIF4A2.
Failed to recover cellular sensitivity following ectopic expression of DDX3X, eIF4A3 or mutant eIF4A1^F163L.

Parmacokinetics

Species	Dose	Route	T_1/2
Mice^[1]	5 mg/kg	p.o.	9.97 h
Mice^[1]	0.5 mg/kg	i.v.	4.11 h

In Vivo

MG-002 (0.5 mg/kg; p.o.; every 3 days) potently inhibits primary TNBC tumor growth in BALB/c mice via reduced cell proliferation and increased apoptosis, with a significant reduction in Myc protein levels^[1].
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.

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]
Dosage:

0.5 mg/kg
Administration:

p.o.; every 3 days
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.

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]
Dosage:

0.5 mg/kg
Administration:

p.o.; every 3 days; until surgical resection
Result:

Significantly reduced the area of spontaneous lung metastases compared to vehicle control.

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]
Dosage:

0.5 mg/kg
Administration:

p.o.; every 3 days; 21 days
Result:

Associated with a modest reduction in established lung tumor burden compared to vehicle control.

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]
Dosage:

0.5 mg/kg
Administration:

p.o.; every 3 days
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.

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]
Dosage:

0.5 mg/kg
Administration:

p.o.; every 3 days
Result:

Significantly reduced established lung tumor burden when combined with doxorubicin compared to both monotherapies and vehicle control.

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]
Dosage:

0.5 mg/kg
Administration:

i.p.; every 2 days
Result:

Delayed growth of MDA-MB-231 tumors.

Chemical Information

CAS. Nr. 3076503-34-6
Molecular Weight 503.50
Formel C₂₇H₂₅N₃O₇
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
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (294 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Cencic R, et al. A second-generation eIF4A RNA helicase inhibitor exploits translational reprogramming as a vulnerability in triple-negative breast cancer. Proceedings of the National Academy of Sciences of the United States of America. 2024 Jan 23;121(4):e2318093121. [Content Brief]

Calculators

Molaritätsrechner

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

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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MG-002

Alle CDK Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Reinheit & Dokumentation

Verweise

Calculators

Help & FAQs

MG-002 Related Classifications

HY-173172 Related Classifications

Bioz