Physicochemical Properties
| Molecular Formula | C28H32CL2N6O3 |
| Molecular Weight | 571.50 |
| Exact Mass | 570.191 |
| CAS # | 2387633-15-8 |
| PubChem CID | 146241691 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 2 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 39 |
| Complexity | 764 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | AZEJIKZNBHEXCM-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C28H32Cl2N6O3/c1-34-6-8-36(9-7-34)28-31-16-24(17-32-28)39-26-11-20(18-35-4-2-19(3-5-35)12-27(37)38)10-25(33-26)21-13-22(29)15-23(30)14-21/h10-11,13-17,19H,2-9,12,18H2,1H3,(H,37,38) |
| Chemical Name | 2-[1-[[2-(3,5-dichlorophenyl)-6-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]oxypyridin-4-yl]methyl]piperidin-4-yl]acetic acid |
| 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) |
Biological Activity
| ln Vitro | BOS-318 (0.001–1 μM, 72 hours) offers cytoprotection against CuFi-1 cytotoxicity caused by Pseudomonas aeruginosa exotoxin A (PEA) [1]. The furin-resistance of BOS-318 (U2OS cells) is roughly 13 times more than that of PCSK5 (IC50 = 25.3 nM), 24 times greater than that of PCSK7 (IC50 = 45.8 nM), and 110 times greater than that of PCSK6 (IC50 = 209.4 nM). [1]. NE and CF sputum sol-mediated ENaC activation is inhibited by BOS-318 (0.3 μM, 2 hours or 48 hours) and ENaC-mediated Na+ uptake in CF HBEC is decreased [1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: CuFi-1 Cell Tested Concentrations: 17.4 and 263.0 nM Incubation Duration: 2 and 48 hrs (hours) Experimental Results: Significant inhibition of ENaC measured in differentiated human bronchial epithelial cells at two short concentration conditions mediated Na+ transport (IC50= 263.0 nM) and long-term (IC50= 17.4 nM) treatment conditions. Cell viability assay[1] Cell Types: CuFi-1 Cell Tested Concentrations: 0.3 μM Incubation Duration: 72 hrs (hours) Experimental Results: Cell viability in PEA-treated cells increased Dramatically to approximately 88% of control levels. Cytotoxicity assay[1] Cell Types: CuFi-1 Cell Tested Concentrations: 0.001, 0.01, 0.03, 0.1, 0.3 and 1 μM Incubation Duration: 72 hrs (hours) Experimental Results: Provides PEA-mediated cytotoxicity against PEA in a dose-dependent manner over time Toxicity protection for 72 hrs (hours) with EC50 of 47.8 nM. |
| References |
[1]. A highly selective, cell-permeable furin inhibitor BOS-318 rescues key features of cystic fibrosis airway disease. Cell Chem Biol. 2022 Jun 16;29(6):947-957.e8. [2]. Clearing the air: Uniquely engaging furin as an approach to cystic fibrosis therapy. Cell Chem Biol. 2022 Jun 16;29(6):927-929. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~87.49 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.37 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 25.0 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: ≥ 2.5 mg/mL (4.37 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 25.0 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.37 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 25.0 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 | 1.7498 mL | 8.7489 mL | 17.4978 mL | |
| 5 mM | 0.3500 mL | 1.7498 mL | 3.4996 mL | |
| 10 mM | 0.1750 mL | 0.8749 mL | 1.7498 mL |