| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
BMS-688521 primarily targets LFA-1 (lymphocyte function-associated antigen-1, also known as CD11a/CD18), an integrin expressed on leukocytes that mediates cell adhesion and migration. By inhibiting the interaction between LFA-1 and ICAM-1, BMS-688521 blocks leukocyte adhesion and migration to sites of inflammation. It has an IC50 of 2.5 nM in the adhesion assay and 60 nM in the MLR assay.
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| ln Vitro |
BMS-688521 in a mouse-specific adhesion assay with mouse splenocytes and the cell line b.END3 that expresses ICAM-1. The human T cell/HUVEC detection data (ICIC50=2.5 nM) is approximately 30 times higher than the IC50 of BMS-688521, which is 78 nM [1].
In vitro, BMS-688521 is a highly potent inhibitor of the LFA-1/ICAM interaction with an IC50 of 2.5 nM in the adhesion assay and 60 nM in the MLR assay. Its activity is characterized by its ability to block LFA-1-mediated adhesion of leukocytes to ICAM-1-expressing cells. The compound's potency and oral activity make it a valuable tool for studying LFA-1 function and for developing anti-inflammatory therapies. |
| ln Vivo |
In a mouse model of allergic eosinophilic lung inflammation, BMS-688521 (1–10 mg/kg; oral; three days BID) can effectively reduce lung inflammation [1]. Cmax, Tmax, AUC, and F values of BMS-688521 (5 mg/kg; oral) were 0.32 μM, 1.0 μM, 1.5 μM h, and 50%, correspondingly [1]. BALB/c mice treated with 1 mg/kg of BMS-688521 (iv) had T1/2, MRT, CL, and Vss values of 1.6 hours, 1.7 hours, 50 mL/mim/kg, and 5.1 L/kg, respectively [1].
In vivo, BMS-688521 is efficacious in a mouse allergic eosinophilic lung inflammation model. This demonstrates its ability to reduce inflammation in a model of allergic airway disease. Its oral activity makes it suitable for in vivo studies. BMS-688521 is a valuable tool for studying LFA-1-mediated inflammation and for developing potential therapies for inflammatory diseases. |
| Enzyme Assay |
The in vitro activity of BMS-688521 is assessed using cell-based adhesion and mixed lymphocyte reaction (MLR) assays. In the adhesion assay, LFA-1-expressing cells are incubated with ICAM-1-coated surfaces in the presence of varying concentrations of BMS-688521. The inhibition of cell adhesion is measured. In the MLR assay, the compound's ability to inhibit T-cell proliferation in response to allogeneic stimulation is measured. The IC50 is determined from dose-response curves.
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| Cell Assay |
For cellular assays, LFA-1-expressing leukocytes (e.g., T cells, monocytes) are cultured in appropriate media. Cells are treated with various concentrations of BMS-688521 (typically 0.1-1000 nM) for defined periods. Cell adhesion to ICAM-1-coated surfaces is assessed. T-cell proliferation is assessed by [³H]thymidine incorporation or CFSE dilution. The expression of activation markers is analyzed by flow cytometry. Cell viability is assessed using standard assays.
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| Animal Protocol |
Animal/Disease Models: BALB/c female mice, 6-8 weeks old (OVA mouse lung inflammation) [1]
Doses: 1, 3 and 10 mg/kg Doses: Oral; three days BID Experimental Results: 1 mg BID /kg dose Dramatically inhibited eosinophil accumulation in a dose-dependent manner at 3 mg/kg and 10 mg/kg. In vivo, BMS-688521 is typically administered orally to animal models of inflammation. In the mouse allergic eosinophilic lung inflammation model, the compound is administered at various doses, and airway inflammation is assessed by measuring eosinophil infiltration, cytokine levels, and histopathological changes in the lungs. Pharmacokinetic studies involve measuring BMS-688521 levels in plasma. Toxicological studies are performed to assess the compound's safety profile. |
| ADME/Pharmacokinetics |
BMS-688521 has a molecular weight of 536.37 g/mol and a molecular formula of C26H19Cl2N5O4. It is a highly potent, orally active inhibitor of the LFA-1/ICAM interaction. The compound should be stored as a powder at -20°C under desiccated conditions. It is soluble in DMSO. Specific pharmacokinetic parameters are not detailed in the provided search results.
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| Toxicity/Toxicokinetics |
Specific toxicity data for BMS-688521 is not available in the provided search results. As an LFA-1 inhibitor, 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 to establish its full safety profile.
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| References | |
| Additional Infomation |
BMS-688521 is a highly potent, orally active inhibitor of the LFA-1/ICAM interaction. It has an IC50 of 2.5 nM in the adhesion assay and 60 nM in the MLR assay. BMS-688521 is efficacious in a mouse allergic eosinophilic lung inflammation model. It is a valuable tool for studying LFA-1-mediated inflammation. The compound is not approved for clinical use and is intended for research purposes only.
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| Molecular Formula |
C26H19CL2N5O4
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| Molecular Weight |
536.37
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| Exact Mass |
535.081
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| CAS # |
893397-44-9
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| PubChem CID |
11699447
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| Appearance |
White to light yellow solid powder
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| LogP |
4.467
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
37
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| Complexity |
971
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CN1C(=O)N(C(=O)[C@]12CN(C[C@H]2C3=CC=C(C=C3)C#N)C4=NC=C(C=C4)C(=O)O)C5=CC(=CC(=C5)Cl)Cl
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| InChi Key |
LILGMDXLRPEBNH-HFZDXXHNSA-N
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| InChi Code |
InChI=1S/C26H19Cl2N5O4/c1-31-25(37)33(20-9-18(27)8-19(28)10-20)24(36)26(31)14-32(22-7-6-17(12-30-22)23(34)35)13-21(26)16-4-2-15(11-29)3-5-16/h2-10,12,21H,13-14H2,1H3,(H,34,35)/t21-,26+/m0/s1
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| Chemical Name |
6-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl]pyridine-3-carboxylic acid
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| Synonyms |
BMS688521; BMS 688521; BMS-688521
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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 : ~100 mg/mL (~186.44 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (9.32 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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: ≥ 5 mg/mL (9.32 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 50.0 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 | 1.8644 mL | 9.3219 mL | 18.6438 mL | |
| 5 mM | 0.3729 mL | 1.8644 mL | 3.7288 mL | |
| 10 mM | 0.1864 mL | 0.9322 mL | 1.8644 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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