| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Dagrocorat targets the glucocorticoid receptor (GR), a nuclear receptor that regulates the transcription of genes involved in inflammation, metabolism, and immune function. As a dissociated glucocorticoid receptor agonist, Dagrocorat selectively modulates GR activity to achieve anti-inflammatory effects while minimizing the side effects associated with traditional glucocorticoids, such as metabolic disturbances, bone loss, and immunosuppression. The compound acts by selectively modulating the glucocorticoid receptor, providing anti-inflammatory benefits without significantly affecting metabolic or bone-related pathways. Dagrocorat's dissociated profile makes it a valuable tool for studying the specific mechanisms of glucocorticoid receptor-mediated anti-inflammatory effects.
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| ln Vitro |
Cytochrome P450 (CYP)3A breaks down dagrocorat into N-oxide metabolites. Reversible inhibitors of several CYPs, including CYP2D6 and CYP3A, include dagrocorat[1].
Dagrocorat demonstrates potent in vitro activity as a glucocorticoid receptor agonist. The compound exhibits anti-inflammatory effects through selective modulation of the glucocorticoid receptor. Dagrocorat's dissociated agonist profile means it can activate anti-inflammatory gene transcription while minimizing the transactivation of genes responsible for metabolic side effects. The compound has been characterized in various in vitro systems, confirming its mechanism of action as a selective glucocorticoid receptor modulator. Detailed cellular activity data, including effects on inflammatory cytokine production and gene expression, are available in the primary literature. |
| ln Vivo |
Dagrocorat has been evaluated in preclinical models for its anti-inflammatory effects. The compound's dissociated glucocorticoid receptor agonist profile suggests it may have therapeutic potential for inflammatory diseases with an improved side effect profile compared to traditional glucocorticoids. Dagrocorat provides anti-inflammatory benefits without significantly affecting metabolic or bone-related pathways. Detailed in vivo efficacy data, including specific model results and dosing regimens, are available in the primary literature. The compound is a valuable tool for studying the role of the glucocorticoid receptor in inflammation and for evaluating dissociated glucocorticoid receptor agonists as therapeutic agents.
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| Enzyme Assay |
The in vitro receptor binding and transactivation assay for Dagrocorat measures the compound's ability to bind to and activate the glucocorticoid receptor. Glucocorticoid receptor binding affinity is assessed using radioligand binding assays with membrane preparations from cells expressing the human glucocorticoid receptor. Varying concentrations of Dagrocorat are incubated with the receptor preparation and a radiolabeled glucocorticoid ligand. The amount of bound radioligand is measured, and binding affinity is determined. For transactivation assays, cells are transfected with a glucocorticoid response element (GRE)-linked reporter gene and treated with varying concentrations of Dagrocorat. Reporter gene activity is measured, and EC50 values are determined. The compound is dissolved in DMSO and diluted in assay buffer. Appropriate positive controls (known glucocorticoid receptor agonists) and negative controls are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for Dagrocorat is performed using cells that express the glucocorticoid receptor and respond to glucocorticoid stimulation, such as immune cells (macrophages, lymphocytes) or fibroblasts. Cells are cultured in appropriate medium and treated with varying concentrations of Dagrocorat or vehicle control (DMSO). Cells are stimulated with inflammatory stimuli (e.g., LPS, TNF-α) to induce pro-inflammatory cytokine production. The effects of Dagrocorat on inflammatory cytokine production (e.g., IL-6, TNF-α, IL-1β) are measured by ELISA or qRT-PCR. The compound's ability to induce anti-inflammatory genes (e.g., IL-10, MKP-1) is also assessed. The selectivity of Dagrocorat for transrepression (anti-inflammatory) versus transactivation (metabolic) pathways can be evaluated by measuring the expression of metabolic genes (e.g., PEPCK, G6Pase).
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| Animal Protocol |
In vivo animal experiments with Dagrocorat are conducted using rodent models of inflammatory diseases, such as collagen-induced arthritis, carrageenan-induced paw edema, or LPS-induced sepsis. Dagrocorat is administered via oral gavage or intraperitoneal injection at various doses. Inflammatory endpoints (e.g., paw swelling, clinical scores, inflammatory cytokine levels) are measured. The compound's effects on metabolic parameters (e.g., blood glucose, insulin, bone density) are also assessed to evaluate its dissociated profile. At study endpoint, tissues are harvested for analysis of glucocorticoid receptor target gene expression and inflammatory markers. The compound's anti-inflammatory efficacy and side effect profile are compared to traditional glucocorticoids.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for Dagrocorat are partially documented. The compound has a molecular weight of 494.56 and a chemical formula of C29H29F3N2O2. Dagrocorat is soluble in DMSO. The compound inhibits CYP3A (human liver microsomes) with an IC50 of 1.3 μM and CYP2D6 with an IC50 of [value not fully shown]. For in vivo administration, the compound is typically formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for Dagrocorat are not extensively documented in publicly available sources. As a research-grade compound, Dagrocorat is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. The compound's dissociated glucocorticoid receptor agonist profile suggests it may have a more favorable side effect profile than traditional glucocorticoids. Comprehensive toxicological profiling is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References | |
| Additional Infomation |
Dagrocorat is a research compound developed for studying the role of the glucocorticoid receptor in inflammation and for evaluating dissociated glucocorticoid receptor agonists as therapeutic agents for inflammatory diseases. The compound is also known as PF-00251802. Dagrocorat is a selective glucocorticoid receptor modulator that exhibits anti-inflammatory effects while minimizing the side effects typically associated with traditional glucocorticoids, such as metabolic disturbances and bone loss. The compound's dissociated profile makes it a valuable tool for dissecting the specific mechanisms of glucocorticoid receptor-mediated anti-inflammatory effects. Dagrocorat is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical research. Dagrocorat is available from various chemical suppliers for research purposes.
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| Molecular Formula |
C29H29F3N2O2
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|---|---|
| Molecular Weight |
494.547978162766
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| Exact Mass |
494.218
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| CAS # |
1044535-52-5
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| Related CAS # |
Dagrocorat hydrochloride;1044535-61-6
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| PubChem CID |
24873449
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| Appearance |
White to off-white solid powder
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| LogP |
6.235
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
36
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| Complexity |
785
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=C(C=CC=N1)NC(=O)C2=CC3=C(C=C2)[C@@]4(CC[C@@](C[C@H]4CC3)(C(F)(F)F)O)CC5=CC=CC=C5
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| InChi Key |
QJJBNCHSWFGXML-QPVYNBJUSA-N
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| InChi Code |
InChI=1S/C29H29F3N2O2/c1-19-25(8-5-15-33-19)34-26(35)22-10-12-24-21(16-22)9-11-23-18-28(36,29(30,31)32)14-13-27(23,24)17-20-6-3-2-4-7-20/h2-8,10,12,15-16,23,36H,9,11,13-14,17-18H2,1H3,(H,34,35)/t23-,27-,28+/m1/s1
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| Chemical Name |
(4bR,7S,8aR)-4b-benzyl-7-hydroxy-N-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-4b,5,6,7,8,8a,9,10-octahydrophenanthrene-2-carboxamide
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| Synonyms |
PF-251802; PF 251802; PF251802; PF-00251802; PF 00251802; PF00251802;
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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 : ~250 mg/mL (~505.51 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (12.64 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 62.5 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: ≥ 6.25 mg/mL (12.64 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 62.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0220 mL | 10.1102 mL | 20.2204 mL | |
| 5 mM | 0.4044 mL | 2.0220 mL | 4.0441 mL | |
| 10 mM | 0.2022 mL | 1.0110 mL | 2.0220 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.
 Clin Pharmacol Drug Dev.2018 Mar;7(3):244-255. |
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 Reversible inhibition of CYP3A activity in pooled human liver microsomes by PF‐00251802 (dagrocorat), using midazolam as a probe substrate.Clin Pharmacol Drug Dev.2018 Mar;7(3):244-255. |
 Mean plasma concentration–time profile for midazolam ± PF‐04171327 (fosdagrocorat).
Time‐dependent inhibition of CYP3A activity in pooled human liver microsomes by (A) PF‐00251802 (dagrocorat) and (B) PF‐04015475, using midazolam as a probe substrate. |
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