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) は、IC50 が 7 nM の強力かつ選択的なヒト非膵分泌性ホスホリパーゼ A2 (hnsPLA) 阻害剤です。現在フェーズ 3 です。
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 of 8.1 nM, 5.0 nM, 3.2 nM and 6.2 nM, respectively. 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. In 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.
in vivo Ex vivo, LY315920 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 ED50 of 16.1 mg/kg. 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.
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
将10 μL的Varespladib (LY315920) DMSO溶液等分加入含有20 μL（10 ng）酶、25 mM Tris·HCl（pH 8）、0.25 mg/mL BSA的溶液中，再加入150 μL含50 mM Tris（pH 8）、0.2 M NaCl、2 mM CaCl2和1 mg/mL无脂肪酸BSA的测定缓冲液。向每管加入20 μL新鲜制备并冰浴保存的PC与胆盐储备液，该储备液经超声处理并配制，以使最终200 μL反应体积中含有3 mM DOC/1 mM总PC以及约1×105 cpm的[14C]PC。为制备脂质底物，将标记PC（1-棕榈酰-2-[14C]-油酰磷脂酰胆碱）、100 mM冷PC氯仿储备液和100 mM DOC（脱氧胆酸钠盐）乙醇溶液混合，氮气流下干燥，再以含0.2 mM NaCl的10 mM Tris重悬，超声处理10分钟。测定管在40°C水浴中孵育1小时。反应通过加入1.5 mL Doles异丙醇/庚烷/0.5 M H2SO4（体积比40:10:1，含1 mg/mL棕榈酸）终止。混合物在60°C加热1分钟，随后加入1 mL H2O和1.25 mL庚烷并充分混合。待两相分离后，转移上清至含150 mg干燥硅胶的1 mL庚烷中，再次混合，1500 g离心5分钟。取上清进行液闪计数，测定释放的[14C]油酸。抑制程度与稀释剂对照比较，并计算抑制浓度。
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
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
Group X secreted phospholipase A(2) induces lipid droplet formation and prolongs breast cancer cell survival. [Pucer A, et al. Mol Cancer, 2013, 12(1):111] PubMed: 24070020

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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