Varespladib (LY315920)

製品コードS1110 バッチS111003

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C21H20N2O5
分子量 380.39 CAS No. 172732-68-2
Solubility (25°C)* 体外 DMSO 76 mg/mL (199.79 mM)
Ethanol 1 mg/mL (2.62 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 0.950mg/ml (2.50mM) Taking the 1 mL working solution as an example, add 50 μL of 19 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Varespladib (LY315920) is a potent and selective human non-pancreatic secretory phospholipase A2 (hnsPLA) inhibitor with IC50 of 7 nM. Phase 3.
in vitro Varespladib (LY315920) exhibits a significant inhibitory effect on sPLA₂ activity in serum from various species including rat, rabbit, guinea pig, and human, with IC₅₀ values of 8.1 nM, 5.0 nM, 3.2 nM, and 6.2 nM, respectively. [2] In BAL cells challenged with human sPLA₂, this compound at doses ranging from 0.1 μM–3 μM reduces the formation of thromboxane mediated by human sPLA₂ in a concentration-dependent manner, with an IC₅₀ of approximately 0.8 μM. [2] In the human conjunctival epithelial cell line (HCjE), it (10 μM) significantly inhibits all-trans-retinoic acid (RA)-induced membrane-associated mucin MUC16 expression by 100% at 24 hours and 99% at 48 hours. [3]
in vivo Varespladib (LY315920), when administered ex vivo at doses ranging from 3 mg/kg to 30 mg/kg via i.v., inhibits human sPLA2-induced release of thromboxane from guinea pig BAL cells with an ED50 of 16.1 mg/kg. [2] In Transgenic Mice Expressing Human sPLA2, both oral and i.v. administration of this compound (0.3 mg/kg–3 mg/kg) abolishes serum sPLA2 activity in a dose and time dependent manner. [2]
特徴 A potent and selective secretory phospholipase A2 inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ DOC/PC Phospholipase A2 Inhibition Assay
Aliquots of 10 μL of Varespladib (LY315920) solutions in DMSO are added to 20 μL (10 ng) of enzyme in 25 mM Tris.HCl (pH 8) with 0.25 mg/mL BSA and 150 μL of assay buffer containing 50mM Tris (pH 8), 0.2 M NaCl, 2 mM CaCl2, and 1 mg/mL fatty acid free BSA. To each tube is added 20 μL of a freshly prepared, iced stock solution of the PC and bile salt, which have been sonicated and concocted such that the final 200 μL reaction volume would contain 3 mM DOC/1 mM total PC and approximately 1 × 105 cpm of [14C]PC. To prepare the lipid substrate, aliquots of labeled PC (1-palmitoyl-2[14C]-oleoylphosphatidyl choline) and 100 mM stock cold PC in chloroform, and 100 mM DOC (sodium salt of deoxycholic acid) in ethanol are mixed, dried under a N2 stream, and then reconstituted in 10 mM Tris with 0.2 mM NaCl, before sonicating for 10 minutes. The assay tubes are incubated for 1 hour in a 40 °C water bath. The reaction is stopped with 1.5 mL of Doles 2-propanol/heptane/0.5 M H2SO4 at 40:10:1 (v/v) with 1 mg/mL palmitic acid. The mixtures are then heated for 1 minute at 60 °C before 1 mL of H2O and 1.25 mL of heptane are added and mixed thoroughly. After the two phases are allowed to separate, the upper phase is transferred to 1 mL of heptane containing 150 mg of dried silica and mixed again before centrifugation for 5 minutes at 1500 g. The supernatant is removed for scintillation counting of the liberated [14C]oleic acid. The degree of inhibition is compared to diluent controls, and the inhibitory concentrations are calculated.
動物実験 動物モデル Transgenic Mice Expressing Human sPLA2 Protein.
投薬量 ≤3 mg/kg
投与方法 Administered via i.v. and p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/8978844/
  • https://pubmed.ncbi.nlm.nih.gov/10027849/
  • https://pubmed.ncbi.nlm.nih.gov/16249480/

カスタマーフィードバック

, , J Am Heart Assoc, 2015, 4:e002553.

, , PLoS One, 2015, 10(4):e0119088.

Data from [Data independently produced by , , Mol Cancer, 2013, 12(1):111.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Exploring Lysophosphatidylcholine as a Biomarker in Ischemic Stroke: The Plasma-Brain Disjunction [ Int J Mol Sci, 2024, 25(19)10649] PubMed: 39408978
The Candida albicans toxin candidalysin mediates distinct epithelial inflammatory responses through p38 and EGFR-ERK pathways [ Front Immunol, 2022, 13:824746] PubMed: 35392090
Substrate-Specific Inhibition Constants for Phospholipase A2 Acting on Unique Phospholipid Substrates in Mixed Micelles and Membranes Using Lipidomics [ J Med Chem, 2019, 62(4):1999-2007] PubMed: 30615445
Substrate-Specific Inhibition Constants for Phospholipase A2 Acting on Unique Phospholipid Substrates in Mixed Micelles and Membranes Using Lipidomics [ J Med Chem, 2019, 62(4):1999-2007] PubMed: 30615445
Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination [Hubler Z, et al. Nature, 2018, 560(7718):372-376] PubMed: 30046109
Novel Role for Matrix Metalloproteinase 9 in Modulation of Cholesterol Metabolism [ J Am Heart Assoc, 2016, 5(10)e004228] PubMed: 27694328
Identification of a Novel Heart–Liver Axis: Matrix Metalloproteinase-2 Negatively Regulates Cardiac Secreted Phospholipase A2 to Modulate Lipid Metabolism and Inflammation in the Liver [Hernandez-Anzaldo S, et al. J Am Heart Assoc, 2015, 4:e002553] PubMed: 26567374
Matrix metalloproteinase-2 negatively regulates cardiac secreted phospholipase A2 to modulate inflammation and Fever. [Berry E, et al. J Am Heart Assoc, 2015, 4(4)] PubMed: 25820137
Cytosolic Phospholipase A2 Modulates TLR2 Signaling in Synoviocytes [Sommerfelt RM, et al. PLoS One, 2015, 10(4):e0119088] PubMed: 25893499
Novel role of group VIB Ca2+-independent phospholipase A2F in leukocyte-endothelial cell interactions: An intravital microscopic study in rat mesentery [Kojima M, et al. J Trauma Acute Care Surg, 2015, 79(5):782-9] PubMed: 26496102

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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