SH458
SH458 is an orally active anti-triple-negative breast cancer compound. SH458 significantly upregulates the expression of unfolded protein response (UPR)-related proteins, including p-eIF2α and p-IRE1α. SH458 induces Apoptosis, G2/M phase arrest, oxidative stress with increased ROS, DNA damage, and checkpoint kinase activation.
For research use only. We do not sell to patients.
- CAS No.: 3109470-77-8
- Formula: C28H30N2O4
- Molecular Weight:458.55
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All DNA/RNA Synthesis Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
eIF2-α |
IRE1α |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-231 | IC50 |
0.23 μM
|
Antiproliferative activity against human MDA-MB-231 cells assessed as viability reduction after 72 hrs incubation by sulforhodamine B (SRB) assay.
Antiproliferative activity against human MDA-MB-231 cells assessed as viability reduction after 72 hrs incubation by sulforhodamine B (SRB) assay.
|
42748754 |
| MDA-MB-468 | IC50 |
0.14 μM
|
Antiproliferative activity against human MDA-MB-468 cells assessed as viability reduction after 72 hrs incubation by sulforhodamine B (SRB) assay.
Antiproliferative activity against human MDA-MB-468 cells assessed as viability reduction after 72 hrs incubation by sulforhodamine B (SRB) assay.
|
42748754 |
| SUM149PT | IC50 |
0.25 μM
|
Antiproliferative activity against human SUM149T/SUM149PT cells assessed as viability reduction after 72 hrs incubation by sulforhodamine B (SRB) assay.
Antiproliferative activity against human SUM149T/SUM149PT cells assessed as viability reduction after 72 hrs incubation by sulforhodamine B (SRB) assay.
|
42748754 |
| 4T1 | IC50 |
0.28 μM
|
Antiproliferative activity against murine 4T1 cells assessed as viability reduction after 72 hrs incubation by sulforhodamine B (SRB) assay.
Antiproliferative activity against murine 4T1 cells assessed as viability reduction after 72 hrs incubation by sulforhodamine B (SRB) assay.
|
42748754 |
| MCF-10A | IC50 |
50 μM
|
Antiproliferative activity against normal human mammary epithelial MCF10A cells assessed as viability reduction after 72 hrs incubation by sulforhodamine B (SRB) assay with IC50 greater than 50 μM.
Antiproliferative activity against normal human mammary epithelial MCF10A cells assessed as viability reduction after 72 hrs incubation by sulforhodamine B (SRB) assay with IC50 greater than 50 μM.
|
42748754 |
In Vitro
SH458 (0.03-3 μM; 7-10 days) selectively inhibited the clonogenic ability of MDA-MB-231 and MDA-MB-468 cells, showing potent inhibition at 0.1 μM, almost complete inhibition at 0.3 μM, while having no effect on MCF10A cells at 3 μM[1].
SH458 (0.13-2 μM; 24 h) activates apoptosis and DNA damage checkpoint signaling in MDA-MB-231 and MDA-MB-468 cells, increasing C-PARP, C-Caspase 3, γH2AX, and CHK1/CHK2 phosphorylation while decreasing Cyclin B1[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 and MDA-MB-468 cells
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Concentration:1 μM
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Incubation Time:24 h
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Result:Induced apoptosis in both MDA-MB-231 and MDA-MB-468 cells in a dose-dependent manner.
At 1 μM, total apoptotic rates reached 45.48% and 45.50%, respectively, representing approximately an 8-fold increase compared with controls.
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Cell Line:MDA-MB-231 and MDA-MB-468 cells
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Concentration:0, 0.125, 0.25, 0.5, 1, 2 μM (concentration course); 1 μM (time course)
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Incubation Time:24 h (concentration course); 0, 3, 6, 12, 24 h (time course)
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Result:Markedly increased phosphorylation levels of eIF2α and IRE1α in both concentration- and time-dependent manners in MDA-MB-231 and MDA-MB-468 cells.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (female, 4-5-week-old)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:i.p.; every 3 days
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Result:SH458 significantly suppressed tumor growth at both 10 and 20 mg/kg compared with the control group and showed greater antitumor efficacy than DOX.
Tumor weights in the SH458-treated groups were markedly lower than those in both the control and DOX groups.
Immunohistochemistry showed that SH458 markedly reduced Ki67 expression in tumor tissues.
SH458 significantly inhibited tumor growth in a dose-dependent manner.
- RNA extraction experimental
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- ROS/oxidative-stress fluorescent staining
- Apoptosis Solutions
- Protocol for Cell Cycle
- Breast Cancer Modeling
- Genotoxicity/Mutagenicity Study
Chemical Information
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CAS No. 3109470-77-8
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Molecular Weight 458.55
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Formula C28H30N2O4
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SMILES
O=C(C1=CN=CC=C1)O[C@H]2CC[C@@]3([H])[C@]4([H])C(C=C5C(C)(C)C(C(C#N)=C[C@]5(C)[C@@]4([H])CC[C@@]32C)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)