| 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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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Rilapladib targets lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme associated with the formation of atherosclerotic plaques. It is a potent inhibitor with an IC₅₀ of 230 pM. It also antagonizes the platelet activating factor receptor (PAFR). Lp-PLA2 is enriched in atherogenic small dense LDL particles.
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| ln Vitro |
By lowering PAF levels and biological activity (as PAF kinase), rilapadib can decrease the manufacture of Lp-PLA2 and avert potential negative effects from Lp-PLA2. [2]
In vitro, Rilapladib potently inhibits Lp-PLA2 activity with an IC₅₀ of 230 pM. By reducing PAF levels and biological activity, it can decrease the manufacture of Lp-PLA2 and prevent potential negative effects from Lp-PLA2. It demonstrates high selectivity for Lp-PLA2 over other phospholipases. |
| ln Vivo |
In vivo, Rilapladib has been investigated for the treatment of atherosclerosis and cardiovascular disease. By inhibiting Lp-PLA2, it holds promise for preventing the formation of fatty streaks (by inhibiting the production of lysophosphatidylcholine), thereby contributing to the treatment of atherosclerosis. It has been studied in clinical trials.
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| Enzyme Assay |
The in vitro enzyme assay for Rilapladib involves measuring the inhibition of Lp-PLA2 activity. Recombinant or purified Lp-PLA2 enzyme is incubated with the compound and a substrate such as platelet-activating factor (PAF) or a synthetic phospholipid. The release of a labeled product is measured to determine enzyme activity. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
In vitro cell-based assays are performed using cell lines that express Lp-PLA2, such as macrophages or other inflammatory cells. Cells are treated with Rilapladib, and Lp-PLA2 activity is measured in cell lysates or conditioned media. The compound's effects on cell function, such as cytokine production or oxidative stress, are also assessed.
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| Animal Protocol |
In vivo animal experiments for Rilapladib have been conducted in models of atherosclerosis, such as ApoE-deficient mice fed a high-fat diet. Animals are administered the compound orally, and atherosclerotic lesion formation is assessed. Plasma Lp-PLA2 activity and lipid profiles are measured. The compound has also been studied in clinical trials for cardiovascular disease.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Rilapladib have been characterized in preclinical species and humans. It is orally bioavailable and achieves sufficient plasma concentrations to inhibit Lp-PLA2 activity. Detailed PK parameters such as half-life, clearance, volume of distribution, and oral bioavailability are determined from plasma concentration-time profiles.
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| Toxicity/Toxicokinetics |
In clinical studies, Rilapladib was generally well-tolerated with an acceptable safety profile. Standard toxicology assessments were conducted to support clinical development. The compound has been evaluated in phase 2 clinical trials for cardiovascular disease. No significant safety concerns were reported that would preclude further development.
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| References |
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| Additional Infomation |
Rilapladib is the third genomics-derived small molecule drug to enter clinical development, developed in collaboration between Human Genome Sciences and GlaxoSmithKline. It is a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. Lp-PLA2 is an enzyme associated with the formation of atherosclerotic plaques.
Drug Indications It has been investigated for the treatment of atherosclerosis and cardiovascular disease.Mechanism of Action Rilapladib is an Lp-PLA2 inhibitor. Studies have found that Lp-PLA2 is enriched in the oxidatively modified, highly atherogenic small dense low-density lipoprotein (LDL) subfractions. Furthermore, Lp-PLA2 enzyme levels are elevated in patients with hyperlipidemia, stroke, type 1 and type 2 diabetes, and postmenopausal women. Therefore, plasma Lp-PLA2 levels are often elevated in individuals considered at risk of developing accelerated atherosclerosis and experiencing clinical cardiovascular events. Therefore, inhibiting the Lp-PLA2 enzyme holds promise for preventing the formation of these fatty streaks (by inhibiting the production of lysophosphatidylcholine), thereby contributing to the treatment of atherosclerosis. Rilapladib was developed in collaboration between Human Genome Sciences and GlaxoSmithKline. It was investigated for the treatment of atherosclerosis and cardiovascular disease. Despite promising preclinical data, clinical development was discontinued. It has not been approved for clinical use. |
| Molecular Formula |
C40H38N3O3F5S
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|---|---|
| Molecular Weight |
735.80502
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| Exact Mass |
735.255
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| CAS # |
412950-08-4
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| PubChem CID |
9918381
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.36g/cm3
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| LogP |
8.335
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
52
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| Complexity |
1200
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NNBGCSGCRSCFEA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C40H38F5N3O3S/c1-51-22-21-46-19-17-32(18-20-46)47(24-27-9-11-28(12-10-27)29-13-15-31(16-14-29)40(43,44)45)37(50)25-48-35-8-3-2-6-33(35)36(49)23-38(48)52-26-30-5-4-7-34(41)39(30)42/h2-16,23,32H,17-22,24-26H2,1H3
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| Chemical Name |
2-[2-[(2,3-difluorophenyl)methylsulfanyl]-4-oxoquinolin-1-yl]-N-[1-(2-methoxyethyl)piperidin-4-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide
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| Synonyms |
SB-659032; GTPL 7376; D05728; SB659032; GTPL-7376; D-05728; SB 659032; GTPL7376;
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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 : ~86.67 mg/mL (~117.79 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (3.06 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 22.5 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: 2.25 mg/mL (3.06 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 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: ≥ 2.25 mg/mL (3.06 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 | 1.3590 mL | 6.7952 mL | 13.5905 mL | |
| 5 mM | 0.2718 mL | 1.3590 mL | 2.7181 mL | |
| 10 mM | 0.1359 mL | 0.6795 mL | 1.3590 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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