CRM1 degrader 1
CRM1 degrader 1 is a CRM1 degrader. CRM1 degrader 1 induces mitochondrial pathway-mediated apoptosis. CRM1 degrader 1 dose-dependently reduces CRM1 protein levels via the ubiquitin-proteasome pathway, promotes nuclear accumulation of p53, and regulates Bcl-2 family proteins and caspase activation. CRM1 degrader 1 is applicable to gastric cancer-related research.
For research use only. We do not sell to patients.
- CAS No.: 2986647-41-8
- Formula: C16H20O3
- Molecular Weight:260.33
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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- References
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Help & FAQs
Biological Activity
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MGC-803 | IC50 |
2.314 μM
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Inhibited MGC803 cell proliferation.
Inhibited MGC803 cell proliferation.
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32810752 |
In Vitro
CRM1 degrader 1 (compound 1l) inhibits the proliferation of MGC803 gastric cancer cells with an IC50 value of 2.314 μM[1].
CRM1 degrader 1 (1.25-10 μM; 24 h) reduces the viability of MGC803 and HGC27 gastric cancer cells in a dose-dependent manner; at 10 μM, the viability of the two gastric cancer cell lines decreases by approximately 40-60%, while almost no toxicity is observed in GES1 normal gastric epithelial cells[1].
CRM1 degrader 1 (1.25-10 μM) reduces the mitochondrial membrane potential (MMP, ΔΨ) of MGC803 and HGC27 cells in a dose-dependent manner[1].
CRM1 degrader 1 dose-dependently reduces CRM1 protein levels and increases p53 protein levels in MGC803 and HGC27 cells[1].
CRM1 degrader 1 (10 μM; 6 h) reduces the co-immunoprecipitation signal of CRM1-p53 in MGC803 cells, promotes the nuclear accumulation of p53 and Ranbp1, and simultaneously decreases the cytoplasmic levels of Ranbp1 and CRM1[1].
The reduction of CRM1 protein in MGC803 and HGC27 cells induced by CRM1 degrader 1 (5 μM; 24 h) is almost completely blocked by MG132 (0.05 μM), supporting that CRM1 degradation depends on the ubiquitin-proteasome pathway[1].
The inhibitory effect of CRM1 degrader 1 on the viability of MGC803 cells is significantly attenuated after p53 siRNA knockdown, which supports the involvement of p53 in the cellular actions of CRM1 degrader 1[1].
CRM1 degrader 1 (1.25-10 μM; 24 h) dose-dependently increases the proportion of Annexin V-positive cells in MGC803 and HGC27 cells, and induces cell apoptosis[1].
CRM1 degrader 1 (1.25-10 μM; 24 h) reduces CRM1 protein levels and increases the levels of p53, cleaved PARP and cleaved caspase-3; it also increases Bax and cleaved caspase-9, and decreases Bcl-2 and Bcl-xL[1].
CRM1 degrader 1 (10 μM; 24 h) acts synergistically with the proteasome inhibitor MG132 (HY-13259) to enhance apoptosis in MGC803 and HGC27 gastric cancer cells; the expression of pro-apoptotic proteins is still upregulated even though the degradation of CRM1 is blocked[1].
Combination treatment with CRM1 degrader 1 (10 μM; 24 h) and MG132 (0.05 μM; 1 h pre-incubation) further enhances apoptosis in MGC803 and HGC27 cells, and increases the levels of p53, cleaved PARP, cleaved caspase-3 and Bax, compared with exposure to either agent alone[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:human gastric cancer cell lines MGC803, HGC27, human gastric epithelial cell line GES1
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Concentration:1.25, 2.5, 5, 10 μM
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Incubation Time:24 h
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Result:Inhibited proliferation of MGC803 cells with an IC50 of 2.314 μM.
Reduced MGC803 and HGC27 cell viability by 40-60% at 10 μM in a dose-dependent manner.
Showed almost no toxicity to GES1 cells.
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Cell Line:human gastric cancer cell lines MGC803 and HGC27
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Concentration:0, 1.25, 2.5, 5, 10 μM
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Incubation Time:24 h
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Result:Increased the number of Annexin V-positive cells in a dose-dependent manner.
Raised apoptotic cells in MGC803 from 3.3% (untreated) to 52.1% at 10 μM.
Raised apoptotic cells in HGC27 from 4.9% (untreated) to 49.3% at 10 μM.
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Cell Line:human gastric cancer cell lines MGC803 and HGC27
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Concentration:0, 1.25, 2.5, 5, 10 μM
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Incubation Time:24 h
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Result:Downregulated CRM1 protein levels in a dose-dependent manner.
Upregulated p53, cleaved PARP, cleaved caspase-3, cleaved caspase-9, and Bax in both cell lines.
Downregulated Bcl-2 and Bcl-xL in both cell lines.
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Cell Line:human gastric cancer cell line MGC803
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Concentration:5 μM (CRM1 degrader 1); 0.05 μM, 0.1 μM MG132, 2.5 nM Bortezomib (HY-10227) (co-incubated)
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Incubation Time:24 h
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Result:Reduced CRM1 protein levels when used alone.
Almost completely abolished CRM1 depletion when co-treated with MG132 or bortezomib.
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Cell Line:MGC803
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Concentration:10 μM
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Incubation Time:6 h
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Result:Increased nuclear accumulation of p53 and Ranbp1.
Chemical Information
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CAS No. 2986647-41-8
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Molecular Weight 260.33
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Formula C16H20O3
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SMILES
CC1=CC(OC[C@H]2CC=CC(O2)=O)=C(C=C1)C(C)C
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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.
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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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.
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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.
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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
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CRM1 degrader 1 Related Classifications
HY-146384 Related Classifications
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