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| Targets |
Furin is a proprotein convertase that activates numerous pathogenic proteins. BOS-318 is a furin inhibitor with an IC50 of 1.9 nM and also inhibits endogenous proteases in U2OS cells with an IC50 of 23.5 nM. It has the characteristics of slow dissociation, high selectivity, and cell permeability, making it effective at inhibiting furin both in biochemical and cellular contexts.
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| 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].
BOS-318 (0.03-1 microM, 72 hours) protects PEA- and CuFi-1 cells from the toxic effects of bacterial toxins activated by furin. In CuFi-1 cells treated with PEA, cell viability was approximately 2% of control levels. A single 0.3 microM dose of BOS-318 significantly increased cell viability to approximately 88% of control levels, demonstrating its potent protective effect against furin-activated toxins. |
| ln Vivo |
No detailed in vivo activity data for BOS-318 are provided in the reference sources beyond in vitro studies. The compound is being developed for cystic fibrosis (CF) lung disease and would likely be tested in animal models of CF lung inflammation, such as beta-ENaC-overexpressing mice or P. aeruginosa infection models, with oral or intratracheal administration.
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| Enzyme Assay |
Furin enzymatic activity is measured using a synthetic peptide substrate containing the furin cleavage sequence (e.g., pERTKR-pNA). For BOS-318, a typical enzyme assay involves incubating 2 nM furin with increasing concentrations of BOS-318 at pH 7.5, adding the fluorescent/colorimetric substrate (5 microM), and monitoring cleavage product formation over time. The IC50 is calculated from dose-response curves.
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| 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. PEA and CuFi-1 cells are seeded in 96-well plates and treated with BOS-318 at concentrations of 0.03, 0.1, 0.3, and 1 microM for 72 hours. After treatment, cell viability is monitored using MTS or CellTiter-Glo assays. The protective effect of BOS-318 against the toxic effects of furin-activated bacterial toxins is assessed by comparing viability of treated vs. control cells. |
| Animal Protocol |
No detailed in vivo animal experimental protocols for BOS-318 are provided in the reference sources. In vivo studies would likely use beta-ENaC-overexpressing CF lung disease model mice or P. aeruginosa infection models. Dosing could be oral or intratracheal at 1-30 mg/kg daily for 1-4 weeks, with assessment of lung inflammation, bacterial clearance, and epithelial function.
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| ADME/Pharmacokinetics |
BOS-318 has a molecular weight of 571.5 and formula C28H32Cl2N6O3. It is soluble in DMSO (100 mg/mL, 174.97 mM). For in vivo studies, it can be formulated as a homogeneous suspension in CMC-Na (≥5 mg/mL) for oral administration. For injection, a 10% DMSO + 40% PEG300 + 5% Tween80 + 45% saline formulation can be used (2 mg/mL).
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| Toxicity/Toxicokinetics |
No detailed toxicity data for BOS-318 are provided in the reference sources. The compound is for research use only. In vitro studies at concentrations up to 1 microM show that BOS-318 protects cells from toxin-induced death rather than causing cytotoxicity, suggesting a favorable safety profile in cell-based assays at the tested concentrations.
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| References | |
| Additional Infomation |
BOS-318 is a research compound currently in preclinical development for cystic fibrosis (CF) lung disease. It rescues key features of CF airway disease by inhibiting furin, which activates ENaC and contributes to airway dehydration in CF. The compound is not yet approved for clinical use. BOS-318 is available for research purposes only.
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| Molecular Formula |
C28H32CL2N6O3
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| Molecular Weight |
571.50
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| Exact Mass |
570.191
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| CAS # |
2387633-15-8
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| PubChem CID |
146241691
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
39
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| Complexity |
764
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCN(CC1)C2=NC=C(C=N2)OC3=CC(=CC(=N3)C4=CC(=CC(=C4)Cl)Cl)CN5CCC(CC5)CC(=O)O
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| InChi Key |
AZEJIKZNBHEXCM-UHFFFAOYSA-N
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| 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)
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| 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
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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 : ~50 mg/mL (~87.49 mM)
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| 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. View More
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. |
| 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 |
*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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