| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
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| Targets |
BI-1467335 HCl targets vascular adhesion protein-1 (VAP-1), also known as semicarbazide-sensitive amine oxidase (SSAO), an enzyme with roles in leukocyte adhesion and transmigration. It inhibits VAP-1 with an IC₅₀ of <100 nM. The compound is selective for VAP-1 over monoamine oxidase B (MAO-B) and diamine oxidase (DAO), with IC₅₀ values of >1,000 nM and >10,000 nM, respectively. By inhibiting VAP-1/SSAO, BI-1467335 HCl reduces leukocyte adhesion and transmigration, thereby attenuating inflammation in various tissues.
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| ln Vitro |
In vitro, BI-1467335 HCl is a selective and potent inhibitor of SSAO/VAP-1 with an IC₅₀ of <100 nM. It shows excellent selectivity over MAO-B (IC₅₀ >1,000 nM) and DAO (IC₅₀ >10,000 nM). The compound's primary mechanism of action involves the inhibition of VAP-1-mediated leukocyte adhesion and transmigration. In cell-based assays, BI-1467335 HCl reduces the migration of neutrophils and other inflammatory cells. The compound has been shown to diminish lung inflammation in a variety of models, indicating proof of concept for a novel therapeutic approach in respiratory diseases characterized by a neutrophilic pattern of inflammation.
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| ln Vivo |
In vivo, BI-1467335 HCl has demonstrated efficacy in several animal models. Oral administration at 10 mg/kg per day reduces plasma total cholesterol, LDL, and glucose levels, as well as decreases the recruitment of macrophages to atherosclerotic lesions and the area of atherosclerotic plaques in a cholesterol-fed rabbit model. The compound reduces neutrophil lung infiltration induced by K. pneumoniae in mice when administered at a dose of 6 mg/kg. It also reduces airway hyperreactivity in a mouse model of rhinovirus-exacerbated allergy-induced asthma. BI-1467335 HCl ameliorates chronic obstructive pulmonary disease in mice. These findings support its potential for treating COPD, NASH, and other inflammatory diseases.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for BI-1467335 HCl involve measuring the inhibition of VAP-1/SSAO enzyme activity. The assay typically uses a fluorogenic or chromogenic substrate that is cleaved by SSAO to produce a detectable signal. Recombinant human VAP-1 is incubated with varying concentrations of BI-1467335 HCl, and the enzyme activity is measured. The IC₅₀ for VAP-1 inhibition is <100 nM. Selectivity profiling is conducted using similar assays with MAO-B and DAO enzymes, showing IC₅₀ values of >1,000 nM and >10,000 nM, respectively. These assays confirm the compound's high selectivity for VAP-1 over other amine oxidases.
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| Cell Assay |
In vitro cell-based assays for BI-1467335 HCl evaluate its effects on leukocyte adhesion and transmigration. Human endothelial cells expressing VAP-1 are cultured and treated with the compound, followed by the addition of fluorescently labeled leukocytes. The adhesion and transmigration of leukocytes across the endothelial monolayer are measured using fluorescence microscopy or flow cytometry. The compound's ability to inhibit SSAO activity in cells can be assessed by measuring the production of hydrogen peroxide or other reaction products. These assays confirm the compound's functional activity in cellular contexts.
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| Animal Protocol |
In vivo animal experiments for BI-1467335 HCl are conducted in various disease models. In a cholesterol-fed rabbit model of atherosclerosis, oral administration at 10 mg/kg per day reduces plasma total cholesterol, LDL, and glucose levels, as well as decreases macrophage recruitment to atherosclerotic lesions and plaque area. In a mouse model of K. pneumoniae-induced lung inflammation, the compound at 6 mg/kg reduces neutrophil infiltration. In a mouse model of rhinovirus-exacerbated allergy-induced asthma, BI-1467335 HCl reduces airway hyperreactivity. The compound also ameliorates COPD in mice. Pharmacokinetic and toxicological parameters are monitored throughout these studies.
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| ADME/Pharmacokinetics |
BI-1467335 HCl is an orally active compound with favorable pharmacokinetic properties. It is soluble in both DMSO and water, facilitating formulation for in vivo studies. The compound has a molecular weight of 316.80 g/mol. Oral administration of BI-1467335 HCl at 10 mg/kg per day achieves therapeutic concentrations in animal models. The compound's metabolic stability and half-life have not been fully characterized in the available literature. For in vivo formulation, the compound can be dissolved in appropriate vehicles for oral or intraperitoneal administration. Comprehensive PK studies are needed to fully characterize its ADME profile.
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| Toxicity/Toxicokinetics |
The toxicity profile of BI-1467335 HCl has been evaluated in preclinical studies. The compound is for research use only and is not intended for human or veterinary use. In animal studies, BI-1467335 HCl has been well-tolerated at therapeutic doses, with no significant adverse effects reported. However, comprehensive toxicological studies, including acute and chronic toxicity, genotoxicity, and carcinogenicity, are needed to fully characterize the safety profile of the compound. Appropriate safety precautions should be taken when handling BI-1467335 HCl in the laboratory.
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| References | |
| Additional Infomation |
BI-1467335 HCl (PXS-4728A) is a selective, orally active inhibitor of semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion protein-1 (VAP-1). It inhibits VAP-1 with an IC₅₀ of <100 nM and is selective over MAO-B (IC₅₀ >1,000 nM) and DAO (IC₅₀ >10,000 nM). The compound has been shown to ameliorate chronic obstructive pulmonary disease in mice and reduce inflammation in various models. It has potential applications in the treatment of NASH, COPD, and other inflammatory diseases. BI-1467335 HCl is for research use only and is not for human or veterinary use.
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| Molecular Formula |
C15H21N2O2F.HCL
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|---|---|
| Molecular Weight |
316.799
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| Exact Mass |
316.135
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| CAS # |
1478364-68-9
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| Related CAS # |
1478364-68-9 (HCl);1478364-40-7;
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| PubChem CID |
71812246
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| Appearance |
White to yellow solid powder
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| LogP |
4.299
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
21
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| Complexity |
342
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)NC(=O)C1=CC=C(C=C1)OC/C(=C/F)/CN.Cl
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| InChi Key |
AEMZEDNMNLIDSL-YGCVIUNWSA-N
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| InChi Code |
InChI=1S/C15H21FN2O2.ClH/c1-15(2,3)18-14(19)12-4-6-13(7-5-12)20-10-11(8-16)9-17;/h4-8H,9-10,17H2,1-3H3,(H,18,19);1H/b11-8+;
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| Chemical Name |
4-[(E)-2-(aminomethyl)-3-fluoroprop-2-enoxy]-N-tert-butylbenzamide;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~250 mg/mL (~789.14 mM)
H2O : ~100 mg/mL (~315.66 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.57 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 20.8 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: ≥ 2.08 mg/mL (6.57 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 20.8 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: ≥ 2.08 mg/mL (6.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 25 mg/mL (78.91 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with heating and sonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1566 mL | 15.7828 mL | 31.5657 mL | |
| 5 mM | 0.6313 mL | 3.1566 mL | 6.3131 mL | |
| 10 mM | 0.3157 mL | 1.5783 mL | 3.1566 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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