ASTX295
Based on 1 Customer Validation
ASTX295 is an orally active and selective MDM2 antagonist with an IC50 of <1 nM. ASTX295 inhibits the MDM2-p53 interaction, activates wild-type TP53, and thereby induces the expression of relevant transcriptional targets, leading to cell death. ASTX295 drives the transition of pancreatic cancer cells from senescence to apoptosis and regulates p53 and DNA damage biomarkers. ASTX295 can be used for the research of hematologic malignancies and pancreatic cancer.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度 : 99.81%
- CAS 番号: 2093449-12-6
- 分子式: C33H34Cl2FNO6
- 分子量:630.53
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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生物活性
製品説明
体外実験
ASTX295 (0-10000 nM; up to 72 h) reduces viability in all tested TP53WT lymphoid malignancy cell lines (DLBCL, MCL, T-cell lymphoma) with IC50 values of <1 nM to 100 nM over up to 72 h, induces p53 and p21 expression, and causes maximal cell death at 72 h (24 h in Z138 cells)[1].
ASTX295 (1 μM; 0-24 h, in combination with a p53 corrector) induces sustained upregulation of p53 signaling and DNA damage-related protein and mRNA biomarkers over a 24-hour period in BxPC3 (TP53: Y220C) cells[2].
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:BxPC3 (TP53: Y220C)
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Concentration:1 μM (in combination with p53 corrector)
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Incubation Time:0, 2, 4, 6, 8, 24 h
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Result:Sustained upregulation of p53, phospho-p53 (S15), MDM2, p21, PUMA, phospho-CHK1 (S345), and phospho-H2A.X (S139) proteins through 24 h.
体内実験
ASTX295 (80 mg/kg; p.o.; single dose) with PC14586 in BxPC3 tumor-bearing mice significantly increases the levels of p53 signaling pathway biomarkers (tissue p21, plasma GDF-15, p21/MDM2/GDF-15 mRNA in tumor tissue, and multiple protein biomarkers)[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BxPC3-tumor bearing mice[2]
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Dosage:80 mg/kg
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Administration:p.o.; single dose; administered 3 hours after 100 mg/kg PC14586 p.o.
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Result:Increased relative tumor p21 levels up to ~45-fold relative to vehicle control at 16 hours post-dose.
Increased human GDF-15 levels in mouse plasma up to ~3.5 ng/ml at 16 hours post-dose, relative to PC14586 alone.
Upregulated tumor p21, MDM2, and GDF-15 mRNA at 16 hours post-dose.
Sustained upregulation of p53 signalling biomarkers (including p-p53 [S15], p21, PUMA, and p-H2A.X [S139]) at 16 hours post-dose by Western blotting.
臨床実験
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
化学情報
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CAS 番号 2093449-12-6
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性状 Solid
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分子量 630.53
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分子式 C33H34Cl2FNO6
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Color White to off-white
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SMILES
CO[C@](C(C(C1=O)=C2)=C(F)C=C2[C@@](CC)(O)C3CCOCC3)(N1[C@H](C4=CC=C(Cl)C=C4)[C@H](C)C(O)=O)C5=CC=C(Cl)C=C5
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
体外:
DMSO : 41.18 mg/mL (65.31 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
プロトコル
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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.
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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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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.
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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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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
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Senescence-associated β-galactosidase staining
Senescence-associated β-galactosidase staining detects β-galactosidase activity that is histochemically visible at pH 6. 0 in senescent cells, where X-gal cleavage produces an insoluble blue precipitate observable by bright-field microscopy. This activity reflects increased lysosomal β-galactosidase/lysosomal mass rather than a senescence-essential enzyme, because GLB1 depletion or genetic lysosomal β-galactosidase deficiency can abolish SA-β-gal staining while cells still undergo senescence. SA-β-gal was originally reported in senescent but not presenescent fibroblasts and keratinocytes, absent from quiescent fibroblasts and terminally differentiated keratinocytes, and increased with donor age in human skin samples. Because SA-β-gal can also appear in some non-senescent or tissue-specific contexts, interpretation should be paired with experimental controls and, when possible, independent senescence markers.
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Genotoxicity/Mutagenicity Study
The bacterial reverse mutation assay detects point mutations that restore amino-acid prototrophy in auxotrophic Salmonella typhimurium or Escherichia coli tester strains; after exposure to a test article, mutagenic activity is read out as an increased number of revertant colonies on minimal agar compared with the vehicle control. The assay uses tester strains with different mutation targets so that base-substitution and frameshift mutagens can be detected, and testing is performed with and without exogenous mammalian metabolic activation because some chemicals require biotransformation to become mutagenic.
純度とドキュメンテーション
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データシート (282 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
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- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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取扱説明書 (2659 KB)
参考文献
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.5860 mL | 7.9298 mL | 15.8597 mL | 39.6492 mL |
| 5 mM | 0.3172 mL | 1.5860 mL | 3.1719 mL | 7.9298 mL | |
| 10 mM | 0.1586 mL | 0.7930 mL | 1.5860 mL | 3.9649 mL | |
| 15 mM | 0.1057 mL | 0.5287 mL | 1.0573 mL | 2.6433 mL | |
| 20 mM | 0.0793 mL | 0.3965 mL | 0.7930 mL | 1.9825 mL | |
| 25 mM | 0.0634 mL | 0.3172 mL | 0.6344 mL | 1.5860 mL | |
| 30 mM | 0.0529 mL | 0.2643 mL | 0.5287 mL | 1.3216 mL | |
| 40 mM | 0.0396 mL | 0.1982 mL | 0.3965 mL | 0.9912 mL | |
| 50 mM | 0.0317 mL | 0.1586 mL | 0.3172 mL | 0.7930 mL | |
| 60 mM | 0.0264 mL | 0.1322 mL | 0.2643 mL | 0.6608 mL |