GR2-128
GR2-128 is a dual inhibitor targeting MLK3 and NAMPT with IC50 values of 84 nM and 14 nM, respectively. GR2-128 inhibits downstream JNK/c‑Jun signaling and reduces NAD+ levels. GR2-128 exhibits antiproliferative and pro-apoptotic activities in triple-negative breast cancer cells without significant toxicity to normal cells. GR2-128 suppresses tumor growth, reduces macrophage and neutrophil infiltration, and increases tumor T-cell markers in a syngeneic mouse model, and can be used for triple-negative breast cancer research.
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- Fòrmula: C27H23N7O2
- Peso molecular:477.52
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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JNK 449 nM (IC50) |
NAMPT 14 nM (IC50) |
MLK3 84 nM (IC50) |
PAK4 |
TrkA |
Caspase 3 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-231 | IC50 |
221 nM
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Inhibits the proliferation of MDA-MB-231 for 72 h.
Inhibits the proliferation of MDA-MB-231 for 72 h.
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42269602 |
| MDA-MB-468 | IC50 |
42 nM
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Inhibits the proliferation of MDA-MB-468 for 72 h.
Inhibits the proliferation of MDA-MB-468 for 72 h.
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42269602 |
| E0771 | IC50 |
42 nM
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Inhibits the proliferation of EO771 for 48 h.
Inhibits the proliferation of EO771 for 48 h.
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42269602 |
GR2-128 inhibits MLK3 and NAMPT in cell-free enzymatic assays with IC50 values of 84 nM and 14 nM, respectively, and shows weak inhibitory activity against JAK2 (IC50 > 20 µM) [1].
GR2-128 inhibits JNK phosphorylation in MLK3-overexpressing MDA-MB-468 cells with an IC50 of 449 nM [1].
GR2-128 reduces NAD⁺ levels in THP-1 cells with an IC50 of 1.88 nM[1].
GR2-128 (72 h) inhibits the proliferation of multiple breast cancer cell lines, with GI50 values of 0.221 µM and 0.042 µM for MDA-MB-231 and MDA-MB-468 cells, respectively[1].
GR2-128 (48 h) inhibits the proliferation of EO771 cells with a GI50 of approximately 42 nM[1].
GR2-128 (1 µM; 24 h) significantly induces apoptosis in MDA-MB-231 cells, while it does not significantly induce apoptosis in normal IMEC cells[1].
GR2-128 (1 µM) exhibits > 90% inhibition against MLK3, MLK1, PAK4, RET, and TRKA in kinase profiling assays[1].
GR2-128 demonstrates favorable metabolic stability in liver microsomes from both species, with T₁/₂ values of 150 min in mouse and 134 min in human liver microsomes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231 cells and IMEC cells
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Concentration:1 µM
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Incubation Time:24 h
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Result:Significantly induced apoptosis in MDA-MB-231 cells, while it did not significantly induce apoptosis in IMEC cells.
| Species | Dose | Route | Cmax |
|---|---|---|---|
| Mice | 10 mg/kg | i.p. | 4250 ng/mL |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Fmale C57BL/6 mice, 2 × 105 cells/mouse orthotopically implanted in the fourth mammary fat pad [1]
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Dosage:10 mg/kg
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Administration:Intraperitoneal injection (i.p.), 5 days a week, for 3 weeks
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Result:Attenuated tumor growth and reduced tumor burden compared to the vehicle control group.
Decreased tumor cell proliferation, as evidenced by a reduction in Ki67-positive cells.
Induced apoptosis in tumor tissues, as demonstrated by increased levels of cleaved caspase-3 and positive TUNEL staining.
Inhibited MLK3 downstream signaling, showing reduced phosphorylation of MLK3, JNK, and c-Jun in tumor tissues by IHC and Western blot analyses.
Decreased tumor infiltration of macrophages (F4/80⁺) and neutrophils (neutrophil elastase⁺).
Increased tumor infiltration of CD3⁺ T cells and CD8⁺ Granzyme B⁺ cytotoxic T cells, while B cell counts (CD19⁺) remained unchanged.
Did not cause significant histopathological changes in vital organs (lung, liver, heart, and kidney) as assessed by H&E staining.
Chemical Information
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Peso molecular 477.52
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Fòrmula C27H23N7O2
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SMILES
O=C(NCCC1=CC=C(NC2=NC(OC3=CC=CC=C3)=C(N=CN4)C4=N2)C=C1)/C=C/C5=CN=CC=C5
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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)
GR2-128 Related Classifications
HY-184396 Related Classifications
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