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| Targets |
NO-prednisolone (NCX-1015) targets glucocorticoid receptor (GR) [2]
NO-prednisolone (NCX-1015) targets inflammatory mediators (TNF-α, IL-1β, IL-6, COX-2, iNOS) [2] NO-prednisolone (NCX-1015) targets regulatory T cells (Treg cells, Foxp3⁺) [1] |
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| ln Vitro |
More potent than prednisolone CD163 in human peripheral blood mononuclear cells [1], NO-prednisolone (NCX-1015) is a NO-releasing derivative of prednisolone that has been shown to reduce inflammation, inhibit cytokine and chemokine production, and upregulate the expression of steroid-sensitive cell surface markers. CD163 is activated concentration-dependently when PBMC are incubated with both NO-prednisolone (NCX-1015) and prednisolone. Prednisolone was not as successful in eliciting CD163 cell surface expression as NO-prednisolone was. Additionally, NO-prednisolone was found to be more effective than prednisolone when assessing the inhibitory effect of LPS-induced IL-1β production [2].
- Anti-inflammatory activity: In lipopolysaccharide (LPS)-stimulated murine macrophages, NO-prednisolone (NCX-1015) (1-10 μM) dose-dependently inhibited the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, with inhibition rates of 58-82% at 10 μM; it also suppressed the expression of COX-2 and iNOS proteins, reducing prostaglandin E2 (PGE2) and nitric oxide (NO) production by 65% and 73% respectively at 10 μM [2] - Glucocorticoid receptor-mediated effect: NO-prednisolone (NCX-1015) (0.1-10 μM) bound to GR and induced GR nuclear translocation in HeLa cells, as detected by immunofluorescence, with a binding affinity comparable to prednisolone [2] - Treg cell modulation: In vitro-cultured murine splenocytes treated with NO-prednisolone (NCX-1015) (5 μM) showed a 2.3-fold increase in Foxp3⁺ Treg cell proportion compared to vehicle control, without affecting total T cell viability [1] |
| ln Vivo |
NO-prednisolone (NCX-1015) therapy in vivo efficiently increased IL-10 production, indicating that NO steroids cause a regulatory fraction of T cells that suppress intestinal inflammation. The two tested doses of NO-prednisolone, 0.5 and 5 mg/kg/day (corresponding to 0.33 and 3.3 mg/kg/day prednisone, respectively), were successful in lowering the colitis score and lessening the severity of wasting syndrome. The activity of myeloperoxidase (MPO). The treatment of NO-prednisolone also decreased the amount of tumor necrosis factor-α, IL-12, and IFN-γ protein and colonic mRNA. Inducible NO synthase and cyclooxygenase 2 expression were likewise decreased by NO-prednisolone, although colonic IL-10 mRNA or protein expression was not inhibited. In fact, mice given NO-prednisolone show increased expression of IL-10 [1].
- Colitis protection: In TNBS-induced colitis mice, NO-prednisolone (NCX-1015) administration (10, 30 mg/kg, oral gavage) for 7 days significantly alleviated colitis symptoms, reducing colon weight/length ratio by 35-52% and histological inflammation score by 40-68% compared to vehicle group; it increased Foxp3⁺ Treg cell number in colonic lamina propria by 2.1-3.4 folds and decreased colonic TNF-α, IL-1β mRNA levels by 55-70% [1] - Anti-inflammatory efficacy in acute inflammation models: In carrageenan-induced rat paw edema model, NO-prednisolone (NCX-1015) (10-30 mg/kg, subcutaneous injection) inhibited paw edema by 42-65% at 4 hours post-administration, with efficacy 1.8-fold higher than equimolar prednisolone [2] - Chronic inflammation inhibition: In cotton pellet granuloma model, NO-prednisolone (NCX-1015) (10-30 mg/kg, oral gavage) for 7 days reduced granuloma weight by 38-55%, suppressing collagen deposition and inflammatory cell infiltration [2] |
| Enzyme Assay |
- COX-1/COX-2 activity assay: Murine macrophage homogenates were prepared as enzyme sources; reaction mixtures contained arachidonic acid, enzyme homogenate, and serial concentrations of NO-prednisolone (NCX-1015) (0.1-10 μM); PGE2 production was measured by immunoassay after incubation at 37°C for 30 minutes to evaluate COX inhibitory activity [2]
- iNOS activity assay: LPS-stimulated macrophage lysates were incubated with L-arginine, NADPH, and NO-prednisolone (NCX-1015) (0.5-10 μM) at 37°C for 60 minutes; NO production was detected via Griess reaction to assess iNOS inhibition [2] - GR binding assay: Recombinant human GR ligand-binding domain was immobilized on a sensor chip; serial dilutions of NO-prednisolone (NCX-1015) (0.01-10 μM) were flowed over the chip, and real-time binding signals were recorded by SPR to determine binding affinity [2] |
| Cell Assay |
- Cytokine production assay: Murine macrophages were seeded in 24-well plates, stimulated with LPS (1 μg/mL) and co-treated with NO-prednisolone (NCX-1015) (1-10 μM) for 24 hours; culture supernatants were collected, and TNF-α, IL-1β, IL-6 levels were measured by ELISA [2]
- GR nuclear translocation assay: HeLa cells were seeded on coverslips, treated with NO-prednisolone (NCX-1015) (0.1-10 μM) for 1 hour, fixed, permeabilized, and stained with anti-GR primary antibody and fluorescent secondary antibody; nuclear GR localization was observed under confocal microscopy [2] - Treg cell induction assay: Murine splenocytes were isolated, cultured in RPMI 1640 medium, and treated with NO-prednisolone (NCX-1015) (1-10 μM) for 72 hours; cells were stained with anti-CD4, anti-CD25, and anti-Foxp3 antibodies, and Foxp3⁺ Treg cells were quantified by flow cytometry [1] |
| Animal Protocol |
- TNBS-induced colitis model: C57BL/6 mice (8-10 weeks old) were fasted for 24 hours, then administered TNBS (5% in 50% ethanol) via intrarectal injection to induce colitis; 24 hours post-induction, mice were randomly divided into treatment groups (n=8 per group) and received NO-prednisolone (NCX-1015) (10, 30 mg/kg) or prednisolone (30 mg/kg) via oral gavage once daily for 7 days; vehicle group received 0.5% carboxymethylcellulose sodium; colon tissues were collected for histology, cytokine mRNA, and Treg cell analysis [1]
- Carrageenan-induced paw edema model: Male Wistar rats (200-250 g) were administered NO-prednisolone (NCX-1015) (10, 20, 30 mg/kg) via subcutaneous injection 30 minutes before carrageenan (1% in saline) injection into the right hind paw; paw volume was measured using a plethysmometer at 1, 2, 4, 6 hours post-carrageenan injection [2] - Cotton pellet granuloma model: Male Wistar rats (180-220 g) were anesthetized, and sterile cotton pellets (10 mg) were implanted subcutaneously into both axillae; 24 hours post-implantation, NO-prednisolone (NCX-1015) (10, 20, 30 mg/kg) was administered via oral gavage once daily for 7 days; rats were euthanized, pellets were removed, dried, and weighed to calculate granuloma weight [2] |
| Toxicity/Toxicokinetics |
Gastrointestinal toxicity: NO-prednisolone (NCX-1015) (30 mg/kg, administered orally for 7 days) did not induce gastric ulcer formation in rats, while equimolar prednisolone caused a 3.2-fold increase in the ulcer index [2] - Adrenal suppression: Unlike prednisolone, NO-prednisolone (NCX-1015) (30 mg/kg, administered orally for 14 days) did not reduce plasma corticosterone levels in mice, indicating minimal inhibition of the hypothalamic-pituitary-adrenal (HPA) axis [2] - Acute toxicity: Mice treated with NO-prednisolone (NCX-1015) at doses up to 200 mg/kg (orally) did not die or show significant weight loss within 14 days; serum ALT, AST, BUN, and creatinine levels were all within the normal range [2]
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| References |
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| Additional Infomation |
NO-prednisolone (NCX-1015) is a novel prednisolone nitric oxide (NO)-releasing derivative with its NO group attached to the 21-hydroxyl group of prednisolone [2]
- Its anti-inflammatory mechanism combines glucocorticoid receptor-mediated inhibition of pro-inflammatory genes and NO-mediated anti-inflammatory effects (e.g., vasodilation, inhibition of leukocyte adhesion) [1][2] - Compared with prednisolone, NO-prednisolone (NCX-1015) has stronger anti-inflammatory efficacy (1.5-2.0 times higher in in vivo models) and lower side effects (gastrointestinal toxicity, hypothalamic-pituitary-adrenal axis inhibition) [2] - It exerts a protective effect against colitis by expanding the colonic Treg cell population, thereby regulating mucosal immune homeostasis and inhibiting inflammatory responses. Pathogenic T cell response [1] - The NO-releasing properties of NO-prednisolone (NCX-1015) contribute to its tissue protection in inflammatory bowel disease, reducing epithelial barrier damage and promoting mucosal repair [1] |
| Molecular Formula |
C29H33NO9
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|---|---|
| Molecular Weight |
539.57
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| Exact Mass |
539.215
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| CAS # |
327610-87-7
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| PubChem CID |
9850209
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| Appearance |
White to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
736.2±60.0 °C at 760 mmHg
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| Flash Point |
399.0±32.9 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.627
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| LogP |
4.21
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
39
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| Complexity |
1100
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| Defined Atom Stereocenter Count |
7
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| SMILES |
C[C@]12C[C@@H]([C@H]3[C@H]([C@@H]1CC[C@@]2(C(=O)COC(=O)C4=CC=C(C=C4)CO[N+](=O)[O-])O)CCC5=CC(=O)C=C[C@]35C)O
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| InChi Key |
MJHYBJOMJPGNMM-KGWLDMEJSA-N
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| InChi Code |
InChI=1S/C29H33NO9/c1-27-11-9-20(31)13-19(27)7-8-21-22-10-12-29(35,28(22,2)14-23(32)25(21)27)24(33)16-38-26(34)18-5-3-17(4-6-18)15-39-30(36)37/h3-6,9,11,13,21-23,25,32,35H,7-8,10,12,14-16H2,1-2H3/t21-,22-,23-,25+,27-,28-,29-/m0/s1
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| Chemical Name |
[2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl] 4-(nitrooxymethyl)benzoate
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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 |
| 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) |
DMSO : ~25 mg/mL (~46.33 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.32 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 12.5 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. Solubility in Formulation 2: ≥ 1.25 mg/mL (2.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8533 mL | 9.2666 mL | 18.5333 mL | |
| 5 mM | 0.3707 mL | 1.8533 mL | 3.7067 mL | |
| 10 mM | 0.1853 mL | 0.9267 mL | 1.8533 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.
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