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| Targets |
BMS-817399 primarily targets the CC chemokine receptor 1 (CCR1), a G protein-coupled receptor that mediates the recruitment of inflammatory cells to sites of inflammation. By antagonizing CCR1, BMS-817399 inhibits chemotaxis induced by various CCR1 ligands. It has CCR1 binding affinity and chemotaxis inhibition potencies of 1 and 6 nM (IC50), respectively. It can be used for the research of rheumatoid arthritis.
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| ln Vitro |
BMS-817399 efficiently suppresses chemotaxis mediated by additional CCR1 ligands in addition to MIP-1α (CCL3) [1].
In vitro, BMS-817399 is a potent CCR1 antagonist with binding affinity and chemotaxis inhibition IC50s of 1 and 6 nM, respectively. It potently inhibits chemotaxis induced by various CCR1 ligands in human THP1 cells with IC50 values ranging from 3.2 to 16.2 nM. Its activity is characterized by its ability to block CCR1-mediated chemotaxis. Its selectivity and potency make it a valuable tool for studying CCR1 function. |
| ln Vivo |
In vivo, BMS-817399 is an orally bioavailable CCR1 antagonist. It has been studied for its potential in rheumatoid arthritis. By inhibiting CCR1-mediated inflammatory cell recruitment, it may reduce inflammation and tissue damage in inflammatory diseases. Further studies are needed to fully characterize its in vivo efficacy and safety in animal models of rheumatoid arthritis and other inflammatory conditions.
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| Enzyme Assay |
The in vitro activity of BMS-817399 is assessed using radioligand binding assays and functional chemotaxis assays. For receptor binding, membrane preparations from cells expressing CCR1 are incubated with a radiolabeled CCR1 ligand in the presence of varying concentrations of BMS-817399. The displacement of the radiolabeled ligand is measured to determine the binding IC50. For functional assays, THP1 cells are treated with BMS-817399 and stimulated with CCR1 ligands.
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| Cell Assay |
For cellular assays, THP1 human monocytic cells are cultured in appropriate media. Cells are treated with various concentrations of BMS-817399 (typically 0.1-100 nM) for defined periods. Chemotaxis is assessed using Transwell chambers with CCR1 ligands as chemoattractants. Calcium flux is measured using fluorescent dyes. The inhibition of CCR1-mediated signaling is measured. Cell viability is assessed using standard assays.
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| Animal Protocol |
In vivo, BMS-817399 is typically administered orally to animal models of rheumatoid arthritis or other inflammatory diseases. The compound is formulated in a suitable vehicle and administered at various doses daily. Efficacy is assessed by measuring paw swelling, joint inflammation, and histological changes in animal models of arthritis. Pharmacokinetic studies involve measuring BMS-817399 levels in plasma. Toxicological studies are performed to assess the compound's safety profile.
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| ADME/Pharmacokinetics |
BMS-817399 has a molecular weight of 454 g/mol and a molecular formula of C23H36ClN3O4. It is a potent, selective, and orally bioavailable CCR1 antagonist. The compound should be stored as a powder at -20°C under desiccated conditions. Specific solubility and pharmacokinetic parameters are not detailed in the provided search results. It is soluble in DMSO and other organic solvents.
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| Toxicity/Toxicokinetics |
Specific toxicity data for BMS-817399 is not available in the provided search results. As a CCR1 antagonist, it may affect the immune system and potentially increase susceptibility to infections. The compound is intended for research purposes only and is not approved for human or veterinary use. Standard laboratory safety precautions should be followed when handling the compound. Comprehensive toxicological studies are required.
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| References | |
| Additional Infomation |
BMS-817399 is currently being investigated in the clinical trial NCT01404585 (a proof-of-concept study of BMS-817399 for the treatment of moderate to severe rheumatoid arthritis).
BMS-817399 is a potent, selective, and orally bioavailable CCR1 antagonist. It exhibits CCR1 binding affinity and chemotaxis inhibition potencies of 1 and 6 nM (IC50), respectively. It potently inhibits chemotaxis induced by various CCR1 ligands. BMS-817399 can be used for the research of rheumatoid arthritis. The compound is not approved for clinical use and is intended for research purposes only. |
| Molecular Formula |
C23H36CLN3O4
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|---|---|
| Molecular Weight |
454.0
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| Exact Mass |
453.239
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| CAS # |
1202400-18-7
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| PubChem CID |
44537841
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
660.7±55.0 °C at 760 mmHg
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| Flash Point |
353.4±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.547
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| LogP |
2.83
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
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| Complexity |
647
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(C)[C@H](C(=O)N1CC[C@@](C(C1)(C)C)(C2=CC=C(C=C2)Cl)O)NC(=O)NCC(C)(C)O
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| InChi Key |
GTDPZONCGOCXOD-JPYJTQIMSA-N
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| InChi Code |
InChI=1S/C23H36ClN3O4/c1-15(2)18(26-20(29)25-13-22(5,6)30)19(28)27-12-11-23(31,21(3,4)14-27)16-7-9-17(24)10-8-16/h7-10,15,18,30-31H,11-14H2,1-6H3,(H2,25,26,29)/t18-,23+/m1/s1
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| Chemical Name |
1-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-(2-hydroxy-2-methylpropyl)urea
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| Synonyms |
BMS817399 BMS 817399 BMS-817399
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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) |
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
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| 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 | 2.2026 mL | 11.0132 mL | 22.0264 mL | |
| 5 mM | 0.4405 mL | 2.2026 mL | 4.4053 mL | |
| 10 mM | 0.2203 mL | 1.1013 mL | 2.2026 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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