Phaeosphaeride A
Phaeosphaeride A is a STAT3 inhibitor with an IC50 of 0.61 mM against human STAT3. It exhibits higher selectivity for STAT3 over STAT1 and STAT5. Phaeosphaeride A inhibits the binding of STAT3 to DNA, STAT3-dependent transcriptional activity, as well as IL-6-induced phosphorylation and signaling of STAT3. Phaeosphaeride A activates the JNK, p38, Akt, CREB and STAT5A/B signaling pathways. Phaeosphaeride A induces oxidative stress (ROS), exerts antiproliferative and growth-inhibitory effects in cancer cells, and shows low cytotoxicity toward non-cancerous cells. Phaeosphaeride A is a phytotoxin and a weak animal toxin, with no antimicrobial activity against tested bacteria and fungi. Phaeosphaeride A can be used in research related to conditions such as cervical cancer and multiple myeloma, as well as weed infestations.
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- CAS No.: 910050-51-0
- Formule: C15H23NO5
- Masse moléculaire:297.35
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Activité biologique
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STAT3 0.61 mM (IC50) |
STAT1 |
STAT5 |
Phaeosphaeride A (>50 μM; 48 h) shows low cytotoxicity against A431 epidermoid carcinoma cells, with an IC50 >50 μM[1].
Phaeosphaeride A (10 μM; 1 h) activates Akt, CREB, JNK, p38, STAT3, and STAT5 signaling pathways in A431 epidermoid carcinoma cells, while not significantly affecting ERK1/2 activation[1].
Phaeosphaeride A inhibits STAT3-DNA binding in a cell-free assay with an IC50 of 0.61 mM and inhibits proliferation of STAT3-dependent U266 cells with an IC50 of 6.7 μM[3].
Phaeosphaeride A (6.25-100 μM; 30 min) inhibits IL-6-induced STAT3Tyr-705 phosphorylation in HeLa cells with an IC50 of 13.5 μM[3].
Phaeosphaeride A inhibits proliferation of HeLa cells with an IC50 of 8.8 μM and MDA-MB-231 cells with an IC50 of 29.7 μM[3].
Phaeosphaeride A (0.1-10 μg/mL) retains anti-proliferative activity against HeLa cells after washout, supporting its ability to form covalent bonds with cellular targets[3].
Phaeosphaeride A selectively inhibits STAT3 DNA binding (IC50 = 0.61 mM) in cell lysate assays, with minimal activity against STAT1 and no activity against STAT5, and is active against STAT3 from HepG2 cells[4].
Phaeosphaeride A inhibits the growth of STAT3-dependent U266 multiple myeloma cells (IC50 = 6.7 μM) and exhibits low micromolar activity against STAT3-independent K562 cells[4].
Phaeosphaeride A (67-84 µM; 48 h) induces necrotic lesions ≥2 mm in size on wounded leaf discs of Cirsium arvense at 67 µM and wounded leaf segments of Elytrigia repens after 48 hours of incubation[5].
Phaeosphaeride A (335 µM; 48 h) exhibits non-selective phytotoxic activity at 335 µM, inducing necrotic lesions on all 10 tested plant species after 48 hours of incubation, with the strongest activity on Triticum aestivum and Elytrigia repens[5].
Phaeosphaeride A (0.335-335 µM; 1-hour soak, followed by 48-hour incubation) inhibits root growth of Raphanus sativus (radish), Lactuca sativa (lettuce), and Cichorium intybus (chicory) seedlings by up to ~58% at 335 µM, with selective activity against radish at the lower concentration of 33.5 µM[5].\n\nWait, correction: the original text uses common names "radish, lettuce, and chicory" without scientific Latin names, so I should not add the scientific names. Let me correct that to follow the zero content alteration rule strictly:\n\nPhaeosphaeride A (0.335-335 µM; 1-hour soak, followed by 48-hour incubation) inhibits root growth of radish, lettuce, and chicory seedlings by up to ~58% at 335 µM, with selective activity against radish at the lower concentration of 33.5 µM[5].
Phaeosphaeride A (40 µM; 3 h) is weakly zootoxic, inhibiting movement in 40% of Paramecium caudatum at 40 µM after 3 hours of incubation[5].
Phaeosphaeride A (48 h) shows increased phytotoxicity on wounded vs. intact Cirsium arvense leaf discs, and its activity is significantly enhanced by adjuvants Hasten (0.1% v/v) and Biopower (0.1% v/v) when dissolved in either 5% DMSO or 5% EtOH, after 48 hours of incubation[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A431 epidermoid carcinoma cells
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Concentration:>50 μM
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Incubation Time:48 h
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Result:Exhibited low cytotoxic activity against A431 cells, with an IC50 value greater than 50 μM.
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Cell Line:HeLa cells
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Concentration:6.25 μM, 12.5 μM, 25 μM, 50 μM, 100 μM
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Incubation Time:30 min
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Result:Inhibited IL-6-induced phosphorylation of STAT3Tyr-705 in HeLa cells.
Chemical Information
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CAS No. 910050-51-0
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Masse moléculaire 297.35
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Formule C15H23NO5
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SMILES
C=C1C2=C([C@@H]([C@@](O)([C@@H](O2)CCCCC)C)O)C(N1OC)=O
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Structure Classification
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Initial Source
Phaeosphaeria avenara
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Abzianidze V, et al. Natural Phaeosphaeride A Derivatives Overcome Drug Resistance of Tumor Cells and Modulate Signaling Pathways. Pharmaceuticals (Basel, Switzerland). 2022 Mar 24;15(4):395. [Content Brief]
[2]. Chatzimpaloglou A, et al. Total synthesis and biological activity of the proposed structure of phaeosphaeride A. The Journal of organic chemistry. 2012 Nov 02;77(21):9659-67. [Content Brief]
[3]. Hirayama Y, et al. Biological evaluation of signal transducer and activator of transcription 3 (STAT3) targeting by phaeosphaeride A and its analogs. Bioorganic & medicinal chemistry letters. 2024 Dec 01;114:130004. [Content Brief]
[4]. Maloney KN, et al. Phaeosphaeride A, an inhibitor of STAT3-dependent signaling isolated from an endophytic fungus. Organic letters. 2006 Aug 31;8(18):4067-70. [Content Brief]
[5]. Poluektova E, et al. Curvulin and Phaeosphaeride A from Paraphoma sp. VIZR 1.46 Isolated from Cirsium arvense as Potential Herbicides. Molecules. 2018 Oct 28;23(11):2795. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)