| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Veliflapon targets the 5-lipoxygenase activating protein (FLAP), a membrane-associated protein essential for the activity of 5-lipoxygenase (5-LO) in leukotriene biosynthesis. It acts as a selective FLAP inhibitor, thereby blocking the synthesis of leukotrienes B4 and C4. The compound is also an inhibitor of leukotriene B4 and C4 synthesis.
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| ln Vitro |
When opsonized zymosan is used to excite mice peritoneal macrophages, Veliflapon (BAY is produced [3].
In vitro, Veliflapon inhibits leukotriene synthesis by blocking FLAP, thereby preventing the production of leukotrienes B4 and C4. It is potent in the rat whole blood ex vivo leukotriene B4 inhibition assay, with ED40 values of 11.8 and 6.7 mg/kg p.o. at 1 and 5 hours, respectively. The compound demonstrates enantioselective potency and validated target engagement. |
| ln Vivo |
Atherogenesis is inhibited by veliflapon (BAY X 1005; DG-031; diet; 18.8 mg/kg/day for 16 weeks) [4]. Veliflapon shows anti-edematous effects in mice's arachidonic acid-induced ear inflammation tests following topical (18 μg/ear) and oral (48.7 mg/kg) dosing [4]. Veliflapon demonstrated efficacy (11.8 and 6.7 mg/kg po at 1 and 5 hours, respectively) and a prolonged half-life (ED40 of 16 hours and 70 mg/kg po) in the rat whole blood isolated leukotriene B4 inhibition assay. 4].
In vivo, Veliflapon is orally active and has a long duration of action, with an ED40 of 16 hours at 70 mg/kg p.o. in the rat whole blood ex vivo leukotriene B4 inhibition assay. It possesses high oral bioavailability (86% in rats). The compound has been studied in animal models of inflammation and asthma, demonstrating efficacy in reducing leukotriene-mediated inflammatory responses. |
| Enzyme Assay |
The in vitro enzyme activity assay for Veliflapon involves measuring its inhibitory effect on 5-lipoxygenase activating protein (FLAP). FLAP is incubated with varying concentrations of Veliflapon and its substrate, arachidonic acid, in the presence of 5-lipoxygenase. Leukotriene B4 and C4 production is measured by ELISA or HPLC. The IC50 for FLAP inhibition is determined from dose-response curves. Veliflapon selectively inhibits FLAP and blocks leukotriene synthesis.
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| Cell Assay |
In vitro cellular assays for Veliflapon involve treating whole blood or isolated leukocytes with varying concentrations of the compound. Cells are stimulated with calcium ionophore or other activators to induce leukotriene synthesis. Leukotriene B4 and C4 levels in the supernatant are measured by ELISA. The compound's potency is assessed by calculating the ED40 for inhibition of leukotriene B4 production. Veliflapon shows ED40 values of 11.8 and 6.7 mg/kg p.o. at 1 and 5 hours in rat whole blood assays.
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| Animal Protocol |
Animal/Disease Models: Female apoE/LDLR-DKO mouse model [4]
Doses: 18.8 mg/kg Route of Administration: diet; one time/day for 16 weeks. Experimental Results: Inhibition of atherosclerosis formation. In vivo animal experiments for Veliflapon typically use rat models of inflammation. The compound is administered orally at various doses (e.g., 70 mg/kg). Whole blood samples are collected at different time points and stimulated ex vivo to measure leukotriene B4 production. The duration of action (ED40 of 16 hours) and oral bioavailability (86% in rats) are assessed. Anti-inflammatory efficacy is evaluated in models of asthma and allergic conditions. |
| ADME/Pharmacokinetics |
Veliflapon possesses high oral bioavailability (86% in rats) and a long duration of action (ED40 of 16 hours). The compound has a molecular weight of 375.44 (C23H21NO4). As an orally active small molecule, it is well-absorbed and has a proven in vivo pharmacokinetic profile. Specific PK parameters including half-life and metabolic pathways are available from preclinical studies.
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| Toxicity/Toxicokinetics |
Veliflapon has been investigated in clinical trials for cardiovascular inflammation and other leukotriene-driven diseases. As a FLAP inhibitor, potential adverse effects may include those related to leukotriene pathway modulation, such as impaired immune responses. The compound's safety profile has been evaluated in preclinical and clinical studies. Complete toxicology data would be available from the compound's development program.
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| References |
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| Additional Infomation |
Veliflapon is being studied in the clinical trial NCT00353067 (Veliflapon (Dg-031) is used to prevent heart attack or stroke in patients with a history of heart attack or unstable angina).
Veliflapon (CAS#: 128253-31-6) is an orally active and selective inhibitor of 5-lipoxygenase activating protein (FLAP), also known as BAY X 1005 and DG-031. It inhibits the synthesis of leukotrienes B4 and C4. Veliflapon possesses high oral bioavailability (86% in rats) and a long duration of action (ED40 of 16 hours). It has been investigated for asthma, allergic conditions, and cardiovascular inflammation. Veliflapon is not approved for clinical use. |
| Molecular Formula |
C23H23NO3
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|---|---|
| Molecular Weight |
361.43362
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| Exact Mass |
361.168
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| CAS # |
128253-31-6
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| Related CAS # |
(S)-Veliflapon;128253-32-7
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| PubChem CID |
123723
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| Appearance |
White to light yellow solid powder
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| Density |
1.242g/cm3
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| Boiling Point |
555.4ºC at 760mmHg
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| Flash Point |
289.7ºC
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| Vapour Pressure |
0mmHg at 25°C
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| Index of Refraction |
1.645
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| LogP |
5.172
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
482
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CCC(C1)[C@H](C2=CC=C(C=C2)OCC3=NC4=CC=CC=C4C=C3)C(=O)O
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| InChi Key |
ZEYYDOLCHFETHQ-JOCHJYFZSA-N
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| InChi Code |
InChI=1S/C23H23NO3/c25-23(26)22(17-6-1-2-7-17)18-10-13-20(14-11-18)27-15-19-12-9-16-5-3-4-8-21(16)24-19/h3-5,8-14,17,22H,1-2,6-7,15H2,(H,25,26)/t22-/m1/s1
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| Chemical Name |
(2R)-2-cyclopentyl-2-[4-(quinolin-2-ylmethoxy)phenyl]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 : ~100 mg/mL (~276.68 mM)
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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 | 2.7668 mL | 13.8339 mL | 27.6679 mL | |
| 5 mM | 0.5534 mL | 2.7668 mL | 5.5336 mL | |
| 10 mM | 0.2767 mL | 1.3834 mL | 2.7668 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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