Cat. No.: 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.

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

CAS No.: 3076503-34-6
Formula: C₂₇H₂₅N₃O₇
Molecular Weight:503.50

Storage:

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

Data Sheet (294 KB)

MG-002 Chemical Structure

CAS No.: 3076503-34-6

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Use of MCE Products

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

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Protocols (14)
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[1]

eIF4A

43 nM (IC₅₀)

Cdk4/cyclin D1

All CDK Isoforms :

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. Further protocols information, click here.

Cell Viability Assay^[1]

View Protocol

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]

View Protocol

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]

View Protocol

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 No. 3076503-34-6
Molecular Weight 503.50
Formula 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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

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

Protocols

All Molecular Biology Cell Biology Animals and Diseases Signal Pathway Related

RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
BrdU Incorporation Assay
Bromodeoxyuridine (BrdU) incorporation assay is based on the principle that BrdU, a thymidine analog, is incorporated into newly synthesized DNA during the S phase of the cell cycle, thereby serving as a marker of DNA replication and cellular proliferation. Incorporated BrdU can be detected using anti-BrdU antibodies following DNA denaturation, enabling visualization or quantification of proliferating cells through immunochemical detection methods such as immunofluorescence or immunohistochemistry.
Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
Protocol for Cell Cycle
Cell-cycle analysis by flow cytometry measures DNA content in single cells to estimate the fraction of cells in G0/G1, S, and G2/M phases. Propidium iodide intercalates into DNA, and after RNA removal with RNase, fluorescence intensity reflects cellular DNA content: 2N cells are assigned to G0/G1, cells between 2N and 4N to S phase, and 4N cells to G2/M. DNA-content analysis alone cannot reliably separate G0 from G1 or G2 from M. Ki-67 can distinguish quiescent G0 cells from cycling cells, EdU or BrdU incorporation marks active DNA synthesis in S phase, and phospho-histone H3 staining identifies mitotic cells within the 4N population.
Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
Flow cytometric DNA-content cell-cycle staining
Flow cytometric DNA-content cell-cycle staining measures the fluorescence intensity of DNA-bound fluorochromes in single cells or nuclei to estimate DNA content distributions, allowing assignment of populations to G0/G1, S, and G2/M phases by DNA histogram deconvolution. Propidium iodide (PI) intercalates into DNA, and PI fluorescence is proportional to cellular DNA content when staining is performed under conditions that make DNA accessible and minimize non-DNA signal. Cells with G2/M DNA content are expected to show approximately twice the fluorescence intensity of G0/G1 cells, while S-phase cells occupy intermediate fluorescence values. PI-based DNA-content analysis can also detect cells with fractional DNA content, often reported as sub-G1, when DNA fragmentation and extraction during staining reduce retained DNA signal in apoptotic cells. DAPI is an alternative DNA fluorochrome for univariate DNA-content analysis, while bivariate approaches combining DNA content with proliferation
Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi

Purity & Documentation

Select Batch:

Purity: 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)

References

[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]

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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

All CDK Isoforms