| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
PF-0251802 targets the glucocorticoid receptor (GR) as a high-affinity partial agonist. As a dissociated agonist, it selectively favors the anti-inflammatory transrepression pathway while reducing deleterious CBP/p300 and Mediator complex recruitment compared to full agonists like dexamethasone. The compound is also a time-dependent reversible inhibitor of CYP3A (IC50=1.3 μM) and CYP2D6 (Ki=0.57 μM).
|
|---|---|
| ln Vitro |
Cytochrome P450 (CYP)3A breaks down dagrocorat hydrochloride to produce its N-oxide metabolite. Reversible inhibitors of several CYPs, including CYP3A and CYP2D6, include dagrocorat hydrochloride[1].
In vitro, PF-0251802 demonstrates high-affinity partial agonism of the glucocorticoid receptor with a differentiated mechanism favoring transrepression over transactivation. It shows prednisolone-comparable anti-inflammatory activity in cell-based assays. The compound also inhibits CYP3A with an IC50 of 1.3 μM and CYP2D6 with a Ki of 0.57 μM as a time-dependent reversible inhibitor. |
| ln Vivo |
In vivo, PF-0251802 demonstrates prednisolone-comparable arthritis suppression in collagen-induced arthritis (CIA) models, with a differentiated bone and glucose safety margin compared to conventional steroidal glucocorticoids. Population pharmacokinetic modeling identifies sex (~26-33% higher clearance in females), weight, and age as covariates, predicting >2-fold AUC variability.
|
| Enzyme Assay |
Specific cell-free enzyme/receptor binding assay protocols for PF-0251802 involve GR binding affinity and functional assays. The compound's high-affinity partial agonism is characterized using radioligand binding displacement assays with recombinant GR. CYP inhibition assays are performed using human liver microsomes with specific probe substrates to determine IC50 (CYP3A) and Ki (CYP2D6) values.
|
| Cell Assay |
In vitro cell-based assays for PF-0251802 use GR-expressing cell lines to assess its partial agonist activity and pathway selectivity. Transrepression and transactivation activities are measured using reporter gene assays, demonstrating preferential activation of the anti-inflammatory transrepression pathway. CYP inhibition is evaluated using human liver microsomes and hepatocytes.
|
| Animal Protocol |
In vivo animal studies for PF-0251802 have been performed in collagen-induced arthritis (CIA) models, where it demonstrates prednisolone-comparable arthritis suppression with improved bone and glucose safety margins. Pharmacokinetic studies in animal models inform the population PK model, identifying sex, weight, and age as covariates affecting drug exposure.
|
| ADME/Pharmacokinetics |
PF-0251802 HCl (Dagrocorat hydrochloride) has a molecular weight of 531.01 g/mol and a molecular formula of C29H30ClF3N2O2. It is soluble in DMSO and appears as a solid powder. Storage: dry, dark, at 0-4°C for short term or -20°C for long term. The compound is orally active and shows good oral bioavailability.
|
| Toxicity/Toxicokinetics |
Specific toxicological data for PF-0251802 are not extensively detailed. The compound is classified for research use only. As a GR modulator, it is designed to have an improved safety margin compared to conventional glucocorticoids, with reduced metabolic and bone side effects. Formal toxicological profiles are not detailed in the available sources.
|
| References | |
| Additional Infomation |
PF-0251802 HCl (CAS 1044535-61-6), also known as Dagrocorat hydrochloride, is an orally active, nonsteroidal selective glucocorticoid receptor modulator (SGRM/SEGRAM) and high-affinity partial GR agonist. It is a dissociated agonist designed to retain anti-inflammatory efficacy while minimizing metabolic and bone side effects. The compound is a CYP3A/CYP2D6 inhibitor.
|
| Molecular Formula |
C29H30CLF3N2O2
|
|---|---|
| Molecular Weight |
531.008917331696
|
| Exact Mass |
530.195
|
| CAS # |
1044535-61-6
|
| Related CAS # |
Dagrocorat;1044535-52-5
|
| PubChem CID |
25157943
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
7.037
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
37
|
| Complexity |
785
|
| Defined Atom Stereocenter Count |
3
|
| 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.Cl
|
| InChi Key |
IHLZSINDEDTWTB-KKVPRZDISA-N
|
| InChi Code |
InChI=1S/C29H29F3N2O2.ClH/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);1H/t23-,27+,28-;/m1./s1
|
| Chemical Name |
(4bS,7R,8aR)-4b-benzyl-7-hydroxy-N-(2-methylpyridin-3-yl)-7-(trifluoromethyl)-5,6,8,8a,9,10-hexahydrophenanthrene-2-carboxamide;hydrochloride
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~188.32 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.5 mg/mL (14.12 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 75.0 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: ≥ 7.5 mg/mL (14.12 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 75.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 7.5 mg/mL (14.12 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8832 mL | 9.4160 mL | 18.8320 mL | |
| 5 mM | 0.3766 mL | 1.8832 mL | 3.7664 mL | |
| 10 mM | 0.1883 mL | 0.9416 mL | 1.8832 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
