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Purity: ≥98%
Cytosporone B (Dothiorelone G; Csn-B) is a naturally occurring octaketide isolated from an endophytic fungus Cytospora sp, acting as an agonist for the nuclear orphan receptor Nur77 (EC50 = 0.278 nM) with antitumor activity. Nuclear orphan receptor Nur77 has important roles in many biological processes. Csn-B binds specifically to the ligand-binding domain of Nur77 with high affinity (IC50=0.278 nM) and stimulates Nur77-dependent transactivational activity towards target genes including Nr4a1 (Nur77) itself, which contains multiple consensus response elements allowing positive autoregulation in a Csn-B-dependent manner. Csn-B also elevates blood glucose levels in fasting C57 mice, an effect that is accompanied by induction of multiple genes involved in gluconeogenesis.
| Targets |
Nur77 (NR4A1, nuclear orphan receptor) (EC50 = 0.8 μM in reporter gene assay for Nur77 activation) [1]
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| ln Vitro |
Cytosporone B specifically enhances Nur77's transactivational activity by targeting the ligand binding region of Nur77. Luciferase activity is induced in cells cotransfected with GAL4-LBD or GAL4-Nur77 by cytosporone B. Cytosporone B's EC50 for Nur77 is 0.278 nM. Cytosporone B exhibits strong pro-apoptotic effects in BGC-823 gastric cancer cells. In 48 hours, cytosporone B treatment causes 63.5% of the cells to undergo apoptosis. Cytosporone B exhibits a targeted action on malignant cells. Cytosporone B has a minor effect on human lung cancer H1299 cells and human hepatoma HepG2 cells, however it reduces the proliferation of human gastric cancer BGC-823 cells and human colon cancer SW620 cells by 470%[1].
1. Cytosporone B acts as a specific agonist for the nuclear orphan receptor Nur77 (NR4A1); it does not activate other nuclear receptors including Nurr1 (NR4A2), Nor1 (NR4A3), ERα, ERβ, AR, GR, MR, PR, TRα, TRβ, RXRα, RARα, PPARγ, LXRα, FXR, or VDR at concentrations up to 10 μM [1] 2. In a GAL4-Nur77 chimeric receptor reporter gene assay, Cytosporone B activated Nur77 with an EC50 of 0.8 μM, and maximum activation was achieved at 5 μM; the activation was dose-dependent and could be blocked by a Nur77 antagonist (THPN) [1] 3. Cytosporone B induced Nur77 translocation from the nucleus to mitochondria in MCF-7 breast cancer cells, triggering cytochrome c release and caspase-3 activation, leading to mitochondrial-mediated apoptosis; this effect was abrogated by Nur77 knockdown via siRNA [1] 4. Cytosporone B inhibited the proliferation of MCF-7, MDA-MB-231, and HeLa cancer cell lines in a dose-dependent manner (IC50 values not specified), with no significant cytotoxicity to normal human mammary epithelial cells (HMECs) at concentrations up to 10 μM [1] |
| ln Vivo |
Treatment with cytosporone B increases the transcriptional activity of the reporter five-fold in the hepatocytes of wild-type mice. When cytosporone B is administered to wild-type mice, blood glucose levels rise noticeably from 3.2 to 11.4 mM in the first 30 minutes[1]. After that, blood glucose levels progressively dropped until they returned to the starting point after 300 minutes.
1. Cytosporone B (dissolved in corn oil) was administered orally to nude mice bearing MCF-7 breast cancer xenografts at a dose of 50 mg/kg once daily for 21 days; it significantly inhibited tumor growth by ~60% compared to vehicle control, with no obvious weight loss or organ toxicity observed in treated mice [1] 2. Immunohistochemical analysis of tumor tissues from Cytosporone B-treated mice showed increased Nur77 expression, elevated cleaved caspase-3 levels, and reduced Ki-67 (proliferation marker) staining, confirming induction of apoptosis and inhibition of tumor cell proliferation in vivo [1] |
| Enzyme Assay |
1. GAL4-Nur77 chimeric receptor reporter gene assay: HEK293 cells were transiently transfected with GAL4-Nur77 (ligand-binding domain) expression plasmid and a GAL4-responsive luciferase reporter plasmid. After transfection, cells were treated with serial dilutions of Cytosporone B (0.1–10 μM) for 24 hours. Luciferase activity was measured using a luminescence assay, and the EC50 value for Nur77 activation was calculated as 0.8 μM. To confirm specificity, cells were co-treated with Cytosporone B and THPN (a Nur77 antagonist), which reversed the luciferase activity induced by Cytosporone B [1]
2. Receptor binding assay for nuclear receptors: Recombinant ligand-binding domains of various nuclear receptors (Nur77, Nurr1, Nor1, ERα, ERβ, etc.) were incubated with Cytosporone B (10 μM) and a radiolabeled specific ligand for each receptor. The amount of bound radioligand was quantified to assess competition; Cytosporone B showed no binding to receptors other than Nur77, confirming its specific interaction with Nur77 [1] |
| Cell Assay |
1. Cancer cell proliferation assay: MCF-7, MDA-MB-231, HeLa cancer cells, and normal HMECs were seeded in 96-well plates and treated with serial concentrations of Cytosporone B (0.1–20 μM) for 48 hours. Cell viability was measured using a colorimetric assay (e.g., MTT assay), and the inhibitory effect on proliferation was calculated. Cytosporone B inhibited cancer cell proliferation in a dose-dependent manner but had minimal effect on HMEC viability at concentrations ≤10 μM [1]
2. Apoptosis detection assay: MCF-7 cells were treated with Cytosporone B (5 μM) for 24 hours, then stained with Annexin V-FITC and propidium iodide (PI). Flow cytometry was used to quantify apoptotic cells, showing a significant increase in early and late apoptotic cells compared to untreated controls. Western blot analysis of cell lysates confirmed cleavage of caspase-3 and release of cytochrome c from mitochondria [1] 3. Nur77 subcellular localization assay: MCF-7 cells were treated with Cytosporone B (5 μM) for 12 hours, then fixed and immunostained with a specific antibody against Nur77. Confocal microscopy was used to visualize Nur77 localization; untreated cells showed nuclear Nur77, while Cytosporone B-treated cells exhibited translocation of Nur77 from the nucleus to mitochondria. siRNA-mediated knockdown of Nur77 abolished this translocation and reversed the apoptotic effect of Cytosporone B [1] |
| Animal Protocol |
The inoculated mice are randomly separated into two groups. One group is given an injection to the abdominal cavity at a dosage of 13 mg/kg of cytosporone B twice a week. The other group is administered with DMSO without cytosporone B. Food consumption and body weight of nude mice are monitored weekly. Four weeks later, the nude mice are killed and the tumors formed are removed, fixed and embedded
Mice 1. MCF-7 breast cancer xenograft model: MCF-7 cells (1×10^7 cells/mouse) were subcutaneously injected into the right flank of female nude mice. When tumors reached a volume of ~100 mm³, mice were randomly divided into treatment and control groups. Cytosporone B was dissolved in corn oil and administered orally at a dose of 50 mg/kg once daily for 21 days; the control group received corn oil alone. Tumor volume was measured every 3 days using calipers (volume = length × width² / 2), and mouse body weight was recorded to monitor toxicity. At the end of the experiment, tumors were excised, weighed, and processed for immunohistochemical analysis (Nur77, cleaved caspase-3, Ki-67 staining) [1] |
| Toxicity/Toxicokinetics |
1. In nude mice, oral administration of 50 mg/kg cytosporin B daily for 21 consecutive days did not result in significant toxicity; no significant weight loss, hepatotoxicity (assessed by serum ALT/AST levels) or nephrotoxicity (assessed by serum creatinine/BUN levels) was observed [1]
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| References | |
| Additional Infomation |
Ethyl 2-[3,5-dihydroxy-2-(1-oxooctyl)phenyl]acetate is an aromatic ketone.
Cytosporone B has been reported in Cytospora, Diaporthe and Phopsis, and relevant data are available. 1. Cytosporone B is a natural product isolated from the fungus Cytospora sp. (number 100725), and was identified by high-throughput screening of Nur77 agonists [1]. 2. Nur77 (NR4A1) is a nuclear orphan receptor with no known endogenous ligand; it plays a dual role in cell survival and apoptosis, and its mitochondrial translocation is a key trigger for cancer cell apoptosis [1]. 3. Cytosporone B is the first small molecule agonist of Nur77. It selectively activates Nur77 and induces mitochondrial-mediated apoptosis in cancer cells without damaging normal cells, providing a new therapeutic strategy for cancer treatment [1]. |
| Molecular Formula |
C18H26O5
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| Molecular Weight |
322.4
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| Exact Mass |
322.178
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| CAS # |
321661-62-5
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| Related CAS # |
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| PubChem CID |
10687292
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.746
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
23
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| Complexity |
368
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
UVVWQQKSNZLUQA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H26O5/c1-3-5-6-7-8-9-15(20)18-13(11-17(22)23-4-2)10-14(19)12-16(18)21/h10,12,19,21H,3-9,11H2,1-2H3
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| Chemical Name |
ethyl 2-(3,5-dihydroxy-2-octanoylphenyl)acetate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.75 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.75 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1017 mL | 15.5087 mL | 31.0174 mL | |
| 5 mM | 0.6203 mL | 3.1017 mL | 6.2035 mL | |
| 10 mM | 0.3102 mL | 1.5509 mL | 3.1017 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
(a) Structures of Csn-B (1) and Csn-C (2). (b) Csn-B stimulates Nur77-dependent transcriptional activity in BGC-823 cells.Nat Chem Biol.2008 Sep;4(9):548-56. |
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(a) Schematic representations of Nur77 and its truncation mutants. (b) Effect of Csn-B on fluorescence quenching of GST-Nur77 and its truncation and site mutants. (c,d) Analysis of Csn-B binding to Nur77 and its LBD by CD spectroscopy (c) and sedimentation equilibrium assay (d) as described inSupplementary Methods.Nat Chem Biol.2008 Sep;4(9):548-56. |
(a) Csn-B stimulates the transactivational activity of GAL4-Nur77 and GAL4-LBD in BGC-823 cells.(b) Effect of siRNA against Nur77 or RXRα on Csn-B–induced transactivational activity.Nat Chem Biol.2008 Sep;4(9):548-56. |
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