| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
BI-653048 phosphate targets the glucocorticoid receptor (GR), a nuclear receptor that mediates the effects of endogenous glucocorticoids like cortisol. It is a selective, non-steroidal agonist of the GR, with an IC50 of 55 nM. By binding to and activating the GR, BI-653048 modulates gene expression, leading to the suppression of pro-inflammatory mediators and the induction of anti-inflammatory proteins. This mechanism underlies its potent anti-inflammatory activity, which is similar to that of corticosteroid drugs but with a non-steroidal structure.
|
|---|---|
| ln Vitro |
BI 653048 represents better drug-like qualities and inhibits CP1A2, CYP2D6, CYP2C9, CYP2C19, and CYP3A4 with IC50 values of 50 µM, 41 µM, 12 µM, 9 µM, and 8 µM, respectively[2]. BI 653048 lowered the affinity to hERG ion channels, with IC50>30 μM, in recombinant HEK293 cells expressing human ERG potassium channels [2]. With an IC50 of 100 nM, BI 653048 suppresses the production of IL-6 in mouse RAW cells when stimulated by TNF[2].
In vitro, BI-653048 is a potent agonist of the glucocorticoid receptor. It has an IC50 of 55 nM for the GR. In cell-based assays, BI-653048 suppresses the production of IL-6 in mouse RAW cells stimulated by TNF-α, with an IC50 of 100 nM. It also inhibits the activity of several cytochrome P450 isoforms, including CYP1A2, CYP2D6, CYP2C9, CYP2C19, and CYP3A4, with IC50 values of 50 µM, 41 µM, 12 µM, 9 µM, and 8 µM, respectively. The compound has a low affinity for the hERG ion channel (IC50 > 30 µM), suggesting a low risk of cardiac toxicity. |
| ln Vivo |
The ED50 value for the total score is 14 mg/kg. BI 653048 (oral; 3, 10, and 30 mg/kg) treatment significantly reduced pannus and bone resorption (33%) as well as the total score (27%), but at high doses (30 mg/kg) all parameters were significantly reduced (87-96%). At 3 mg/kg, there was no significant reduction in any of the measured histological parameters (ankle joint inflammation, pannus formation, cartilage damage, and bone resorption).
In vivo, BI-653048 has demonstrated anti-inflammatory efficacy. In mouse models, oral administration of BI-653048 at doses of 3, 10, and 30 mg/kg significantly reduced pannus formation and bone resorption. The ED50 value for the total score was 14 mg/kg. At high doses (30 mg/kg), all measured histological parameters, including ankle joint inflammation, pannus formation, cartilage damage, and bone resorption, were significantly reduced (87-96%). These findings confirm the potent anti-inflammatory activity of BI-653048 in vivo. |
| Enzyme Assay |
In vitro receptor binding assays for BI-653048 phosphate measure its affinity for the glucocorticoid receptor. Membranes from cells expressing the GR are incubated with a radiolabeled GR ligand and varying concentrations of the compound. The Ki is determined from competition binding curves. Functional assays measure the compound's ability to activate GR-mediated transcription. Cells are transfected with a glucocorticoid response element (GRE)-luciferase reporter and treated with the compound. The EC50 for transcriptional activation is determined. These assays confirm the compound's activity as a GR agonist.
|
| Cell Assay |
In vitro cell-based assays for BI-653048 phosphate are used to study its anti-inflammatory effects. Immune cells, such as macrophages, are treated with the compound and then stimulated with an inflammatory stimulus like TNF-α. The production of pro-inflammatory cytokines, such as IL-6, is measured by ELISA. The compound's ability to suppress cytokine production is assessed. These assays confirm the compound's cellular activity as a GR agonist and its potent anti-inflammatory effects.
|
| Animal Protocol |
Animal/Disease Models: Mice[2] Doses: 3, 10 and 30 mg/kg
Route of Administration: Oral Experimental Results: All measured histological parameters were Dramatically diminished at high doses. In vivo animal experiments for BI-653048 phosphate have been conducted in mouse models of inflammation. In a typical study, the compound is administered orally to mice with induced inflammation, and histological parameters are assessed. The ED50 value for the total score was 14 mg/kg. At 30 mg/kg, the compound significantly reduced pannus, bone resorption, and total score. These studies provide evidence for the in vivo efficacy of BI-653048 phosphate as an anti-inflammatory agent. |
| ADME/Pharmacokinetics |
BI-653048 phosphate has a molecular weight of 613.52 g/mol and a molecular formula of C23H28F4N3O8PS. It is a white to off-white solid powder with a purity of ≥98%. For storage, it is recommended to keep the powder at -20°C. Pharmacokinetic properties have been characterized in preclinical studies. BI-653048 is orally active. Detailed pharmacokinetic parameters, such as half-life and bioavailability, are available from these studies.
|
| Toxicity/Toxicokinetics |
Detailed toxicity data for BI-653048 phosphate is not provided in standard product descriptions. However, its activity against CYP450 enzymes suggests potential for drug-drug interactions. Its low affinity for the hERG ion channel (IC50 > 30 µM) suggests a low risk of cardiac toxicity. As a GR agonist, it may have side effects similar to those of corticosteroids, such as immunosuppression and metabolic disturbances. As with all research chemicals, standard laboratory safety precautions should be followed when handling BI-653048 phosphate.
|
| References | |
| Additional Infomation |
BI-653048 phosphate is a research compound and is not approved for any clinical or therapeutic use. It is a selective, oral, non-steroidal glucocorticoid (GC) agonist. It was developed as a potential therapeutic agent for inflammatory diseases. Its mechanism of action involves activating the glucocorticoid receptor, leading to the suppression of pro-inflammatory mediators. It has been disclosed in patent WO2005028501A1 as compound 103. BI-653048 phosphate is a valuable research tool for studying glucocorticoid receptor signaling and inflammation.
|
| Molecular Formula |
C23H28F4N3O8PS
|
|---|---|
| Molecular Weight |
613.51609992981
|
| Exact Mass |
515.15
|
| CAS # |
1198784-72-3
|
| Related CAS # |
BI 653048 phosphate;1198784-97-2
|
| PubChem CID |
44543970
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.7
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
35
|
| Complexity |
879
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
S(CC)(C1=CC2=C(C=N1)NC(=C2)C[C@@](C(F)(F)F)(CC(C)(C)C1C=CC(=CC=1C(N)=O)F)O)(=O)=O.P(=O)(O)(O)O
|
| InChi Key |
AUIFRJWXYUNPPV-QFIPXVFZSA-N
|
| InChi Code |
InChI=1S/C23H25F4N3O4S/c1-4-35(33,34)19-8-13-7-15(30-18(13)11-29-19)10-22(32,23(25,26)27)12-21(2,3)17-6-5-14(24)9-16(17)20(28)31/h5-9,11,30,32H,4,10,12H2,1-3H3,(H2,28,31)/t22-/m0/s1
|
| Chemical Name |
2-[(4R)-4-[(5-ethylsulfonyl-1H-pyrrolo[2,3-c]pyridin-2-yl)methyl]-5,5,5-trifluoro-4-hydroxy-2-methylpentan-2-yl]-5-fluorobenzamide
|
| Synonyms |
BI 653048 BI-653,048 BI653,048 BI 653,048BI-653048 BI653048 BI-653048 phosphate
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6299 mL | 8.1497 mL | 16.2994 mL | |
| 5 mM | 0.3260 mL | 1.6299 mL | 3.2599 mL | |
| 10 mM | 0.1630 mL | 0.8150 mL | 1.6299 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02217631 | COMPLETED | Drug: BI 653048 BS H3PO4 Drug: Prednisolone low dose Drug: Prednisolone high dose Drug: Placebo |
Healthy | Boehringer Ingelheim | 2009-10 | Phase 1 |
| NCT02224105 | COMPLETED | Drug: BI 653048 BS Drug: Prednisolone low Drug: Prednisolone high |
Healthy | Boehringer Ingelheim | 2010-03 | Phase 1 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
