| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| ln Vitro |
Verducatib (BI 1291583) (0.08, 0.4, 2, 10, 50 nM, pH 4.5) binds reversibly covalently to recombinant human cathepsin C (CatC). Its binding kinetic parameters are: kon 6.36×10⁶ M⁻¹s⁻¹, koff 2.29×10⁻³ s⁻¹, equilibrium dissociation constant KD is 0.43 nM, and binding half-life t₁/₂ is 5.19 min[3]. Verducatib (0.064-1000 nM; 48 h) inhibits the production of active neutrophil elastase (NE) in human neutrophil progenitor cells U937 in a concentration-dependent manner, with an IC₅₀ of 0.7 nM. It has no obvious cytotoxicity to U937 cells, and the cell survival rate is higher than 93% at all tested concentrations, with an average cell survival rate of 98% at the highest concentration of 1000 nM[3].
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| ln Vivo |
In a lipopolysaccharide (LPS)-induced lung neutrophil infiltration model in female Cr1:NMRI mice, Verducatib (BI 1291583) (0.005–5 mg/kg; orally; twice daily) dose-dependently inhibited the production of active neutrophil elastase (NE) and cathepsin G (CatG) in bronchoalveolar lavage fluid (BALF), with maximum inhibition rates of 97% and 99%, respectively. The ED99 for NE inhibition was 1.5 mg/kg [3]. In pharmacokinetic models in healthy mice and rats, Verducatib (single oral dose) rapidly distributed to the target tissue, bone marrow, and was slowly cleared. Even at low doses, its distribution profile showed significantly higher bone marrow exposure than plasma exposure, and this characteristic was not significantly different between the two species [3].
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| Cell Assay |
ELISA detection [3]
Cell Types: Human neutrophil progenitor cells U937 Tested Concentrations: 0.064, 0.32, 1.6, 8, 40, 200, 1000 nM Incubation Duration: 48 hours Experimental Results: Inhibited the production of active neutrophil elastase (NE) in human neutrophil progenitor cells U937, with an IC50 of 0.7 nM. |
| Animal Protocol |
Animal/Disease Models:Female Cr1:NMRI mice, LPS-stimulated pulmonary neutrophil infiltration model, used for preclinical mechanism verification of bronchiectasis [3]
Doses: 0.005 mg/kg, 0.05 mg/kg, 0.5 mg/kg, 5 mg/kg Route of Administration: twice daily by gavage on days 1-5, 8 and 9, with the last administration on day 10, followed by nebulized Escherichia coli LPS stimulation Experimental Experimental Results: The production of active neutrophil elastase (NE) and cathepsin G (CatG) in bronchoalveolar lavage fluid (BALF) neutrophils was inhibited in a dose-dependent manner. The maximum inhibition rate of NE reached 97%, and the ED99 value of NE inhibition was 1.5 mg/kg; the maximum inhibition rate of CatG reached 99%. Compared with the solvent control group, NE activity was statistically significantly inhibited (p<0.001). Five hours after the last administration of 0.5 mg/kg, the mean exposure of BI 1291583 in bone marrow was 2981.7 nM, while the corresponding plasma exposure was 32.5 nM. |
| References |
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| Molecular Formula |
C31H35FN4O3
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|---|---|
| Molecular Weight |
530.63
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| CAS # |
1887236-33-0
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| Appearance |
White to off-white solid
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| SMILES |
FC1=C(C[C@@H](C#N)NC([C@@H]2[C@]3([H])C[C@](CC3)([H])N2)=O)C=CC(C4=CC=C5COC6(CCN(C7COC7)CC6)C5=C4)=C1
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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 (~94.23 mM; with sonication)
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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 | 1.8846 mL | 9.4228 mL | 18.8455 mL | |
| 5 mM | 0.3769 mL | 1.8846 mL | 3.7691 mL | |
| 10 mM | 0.1885 mL | 0.9423 mL | 1.8846 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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