LY315920 (Varespladib) is a potent and selective secretory phospholipase A2 (sPLA) inhibitor with IC50 of 7 nM. LY315920 inhibited sPLA2 activity with an IC50 of 9 +/- 1 nM or 7.3 x 10(-6) mole fraction, which approached the stiochiometric limit of this assay in a chromogenic isolated enzyme assay. LY315920 (Varespladib) was 40-fold less active against human, group IB, pancreatic sPLA2 and was inactive against cytosolic PLA2 and the constitutive and inducible forms of cyclooxygenase. The i.v. administration of LY315920, 5 min before harvesting the bronchoalveolar lavage cells, resulted in the inhibition of sPLA2-induced production of TXA2 with an ED50 of 16.1 mg/kg. LY315920 (Varespladib) is currently undergoing clinical evaluation and should help to define the role of sPLA2 in various inflammatory disease states.
| Cell Experiment | |
|---|---|
| Cell lines | |
| Preparation method | |
| Concentrations | |
| Incubation time | |
| Animal Experiment | |
|---|---|
| Animal models | Transgenic Mice Expressing Human sPLA2 Protein |
| Formulation | 5% DMSO, 5% ethanol, and 30% polyethylene glycol 300 in water |
| Dosages | 0.3–3 mg/kg |
| Administration | i.v. |
| Molecular Weight | 380.39 |
| Formula | C21H20N2O5 |
| CAS Number | 172732-68-2 |
| Solubility (25°C) | DMSO 75 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related Phospholipase Products |
|---|
| Phospholipase A2
Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid (AA). |
| Melittin
Melittin is a PLA2 activator that stimulates the activity of low molecular weight PLA2 without increasing the activity of high molecular weight PLA2. |
| trans-4-phenylbut-3-en-2-one
trans-Benzylideneacetone (trans-Benzalacetone), a metabolite of gram-negative entomopathogenic bacterium Xenorhabdus nematophila, is an enzyme inhibitor against phospholipase A2 (PLA2). |
| SYN-020
SYN-020 is an orally active recombinant bovine intestinal alkaline phosphatase (IAP) for studies related to digestive disorders. |
| IIAEK
IIAEK is a novel cholesterol-lowering pentapeptide derived from bovine milk β-lactoglobulin that targets intestinal alkaline phosphatase (IAP) and improves cholesterol metabolism through the specific activation of IAP and down-regulation of ABCA1. Sequence: Ile-Ile-Ala-Glu-Lys |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
