AZD2716
Based on 1 Customer Validation
AZD2716 is an orally active secretory phospholipase A2 (sPLA2) inhibitor. AZD2716 inhibits human GIIA sPLA2 (IC50=10 nM), human GV sPLA2 (IC50=40 nM), human GX sPLA2 (IC50=400 nM), snake venom sPLA2 (IC50=2 pM), and snake (Bothrops jararacussu) Lys49-PLA2-like toxin (Kd=110 μM). AZD2716 inhibits sPLA2 isoforms IIa, V, X, snake venom sPLA2s, and snake venom Lys49-PLA2-like toxin myotoxic activity via hydrophobic channel binding. AZD2716 suppresses GIIA sPLA2 production, neutralizes snake venom-induced myotoxicity, and improves survival in envenomed mice. AZD2716 can be used for the research of coronary artery disease, atherosclerosis, and snakebite envenoming.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度 : 99.9%
- CAS 番号: 1845753-81-2
- 分子式: C24H23NO3
- 分子量:373.44
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保管条件:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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溶剤 & 溶解度
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
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生物活性
製品説明
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sPLA2 |
GIIA sPLA2 10 nM (IC50) |
GV sPLA2 40 nM (IC50) |
GX sPLA2 400 nM (IC50) |
snake venom sPLA2 2 pM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HepG2 | IC50 |
<14 nM
Compound: (R)-7; AZD2716
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Inhibition of sPLA2 in human HepG2 cells
Inhibition of sPLA2 in human HepG2 cells
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[PMID: 27774123] |
| HepG2 | IC50 |
176 nM
Compound: (R)-7; AZD2716
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Inhibition of sPLA2-2A production in human HepG2 cells
Inhibition of sPLA2-2A production in human HepG2 cells
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[PMID: 27774123] |
体外実験
AZD2716 potently inhibits plasma sPLA2 with an IC50 of 0.1 nM[1].
AZD2716 (266 nM-2.18 mM; 5 min) binds to BthTX-I with a dissociation constant (Kd) of 110 μM, demonstrating micromolar-range affinity[2].
AZD2716 (6.5 mg/mL; ~15 days, 300 ns) binds to the hydrophobic channels of dimeric PrTX-I (two inhibitor molecules per toxin dimer), preventing fatty acid access and full toxin activation stabilization, with stable binding maintained over 300 ns of molecular dynamics simulation[2].
AZD2716 (up to 25 μM) does not inhibit OATP1B1-mediated pivastatin uptake in OATP1B1-transfected HEK293 cells at concentrations up to 25 μM[3].
AZD2716 has an intrinsic clearance of 12 μL/min/106 cells in primary human hepatocytes[3].
AZD2716 potently inhibits purified human sPLA2-IIa, sPLA2-V, and sPLA2-X enzymes with IC50 values of 0.010 μM, 0.040 μM, and 0.400 μM, respectively, and inhibits human plasma sPLA2 activity with an ICu,50 of 0.1 nM[3].
AZD2716 inhibits sPLA2 activity in HepG2 cells with an IC50 < 14 nM and suppresses sPLA2-II production in HepG2 cells with an IC50 of 176 nM[3].
AZD2716 inhibits sPLA2 activity in human carotid atherosclerotic plaque homogenates with an IC50 of 56 nM[3].
AZD2716 potently inhibits multiple sPLA2 isoforms (GIIA, GV, GX) in cell-free assays, and inhibits sPLA2 activity in human plasma and atherosclerotic plaque homogenates, with IC50 values ranging from 0.1 nM to 400 nM[4].
AZD2716 inhibits sPLA2 activity and suppresses GIIA sPLA2 production in HepG2 cells, with IC50 values of <14 nM and 176 nM, respectively[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | AUC0-inf | CL | Vss | F |
|---|---|---|---|---|---|---|
| Mice[3] | 10 μmol/Kg | i.v. | 69.7 μM·h | 9.2 mL/min/kg | 2.8 L/kg | 76.3 % |
| Mice[3] | 50 μmol/Kg | p.o. | 69.7 μM·h | 9.2 mL/min/kg | 2.8 L/kg | 76.3 % |
| Rat[3] | 2 μmol/Kg | i.v. | 70 μM·h | 1 mL/min/kg | 0.21 L/kg | 84 % |
| Rat[3] | 8 μmol/Kg | p.o. | 70 μM·h | 1 mL/min/kg | 0.21 L/kg | 84 % |
| Dog[3] | 1 μmol/Kg | i.v. | 284.1 μM·h | 0.2 mL/min/kg | 0.15 L/kg | 91 % |
| Dog[3] | 3 μmol/Kg | p.o. | 284.1 μM·h | 0.2 mL/min/kg | 0.15 L/kg | 91 % |
| Cynomolgus Monkey[3] | 5 μmol/Kg | i.v. | 71.3 μM·h | 2.8 mL/min/kg | 1.1 L/kg | 81 % |
| Cynomolgus Monkey[3] | 15.8 μmol/Kg | p.o. | 71.3 μM·h | 2.8 mL/min/kg | 1.1 L/kg | 81 % |
体内実験
AZD2716 (5-10 mg/kg; i.v., single dose within 10 minutes of envenoming; p.o., two doses first within 10 minutes second at 6 hours) significantly improves survival in envenomed mice versus venom-only controls, with greater efficacy against viper venoms than elapid venoms, but provides a weaker survival benefit than Varespladib (HY-13402)[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Cynomolgus monkey[3]
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Dosage:30 mg
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Administration:p.o.; single dose
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Result:Generated concentration-dependent inhibition of plasma sPLA2 activity, with an unbound concentration required for 80% inhibition (ICu,80) of 13 nM.
Maintained high inhibition for up to 24 hours.
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Animal Model:CD-1 (male, body weight 24.8-35 g, envenomed via subcutaneous or intraperitoneal injection with snake venom)[5]
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Dosage:5 mg/kg (i.v.); 10 mg/kg (p.o.)
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Administration:i.v.; single dose; within 10 minutes of envenoming; p.o.; two doses (first within 10 minutes, second at 6 hours)
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Result:Significantly improved survival versus venom-only controls (χ2 = 5.93, p < 0.05).
Provided a minimal ΔRMST of +44 minutes against elapid venoms and +524 minutes against viper venoms with intravenous administration.
Yielded a ΔRMST of +155 minutes against elapid venoms and +535 minutes against viper venoms with oral administration.
Resulted in a ΔRMST of -8 minutes (95% CI -53 to 14) with IV administration and 16 minutes (95% CI 15 to 16) with PO administration against M. fulvius venom, with no significant survival improvement.
Resulted in a ΔRMST of 96 minutes (95% CI 20 to 174) with IV administration and 293 minutes (95% CI 18 to 562) with PO administration against O. scutellatus venom, with no animals surviving to the end of the study.
Resulted in a ΔRMST of 556 minutes (95% CI 231 to 847) with IV administration and 700 minutes (95% CI 457 to 882) with PO administration against C. scutulatus venom, with 2-3 deaths per group of 5 mice.
Resulted in a ΔRMST of 212 minutes (95% CI -69 to 461) with IV administration and 170 minutes (95% CI -162 to 446) with PO administration against D. russelii= venom.
化学情報
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CAS 番号 1845753-81-2
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性状 Solid
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分子量 373.44
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分子式 C24H23NO3
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Color White to off-white
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SMILES
NC(C1=C(C2=CC(C[C@@H](C)C(O)=O)=CC=C2)C=C(C=C1)CC3=CC=CC=C3)=O
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
体外:
DMSO : 10 mg/mL (26.78 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
純度とドキュメンテーション
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データシート (279 KB)
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SDS (393 KB)
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- Portuguese - PT (393 KB)
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取扱説明書 (2659 KB)
参考文献
[1]. Silverman JE. In This Issue, Volume 7, Issue 10. [Content Brief]
[2]. Salvador GHM, et al. Structural and pharmacological analysis of a PLA2-like toxin in complex with the sPLA2 inhibitor AZD2716: Comparisons to varespladib. Biochimie. 2026;245:120-131. [Content Brief]
[3]. Giordanetto F, et al. Discovery of AZD2716: A Novel Secreted Phospholipase A2 (sPLA2) Inhibitor for the Treatment of Coronary Artery Disease. ACS Med Chem Lett. 2016;7(10):884-889. Published 2016 Aug 9. [Content Brief]
[4]. Batsika CS, et al. The design and discovery of phospholipase A2 inhibitors for the treatment of inflammatory diseases. Expert Opin Drug Discov. 2021;16(11):1287-1305. [Content Brief]
[5]. Hearth JL, et al. In vitro-in vivo discord: A preclinical study of AZD2716 and its racemate with comparison to varespladib for the development of snake venom sPLA2 inhibitors. Toxicon: X. 2026 Feb 12:100243. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.6778 mL | 13.3890 mL | 26.7781 mL | 66.9452 mL |
| 5 mM | 0.5356 mL | 2.6778 mL | 5.3556 mL | 13.3890 mL | |
| 10 mM | 0.2678 mL | 1.3389 mL | 2.6778 mL | 6.6945 mL | |
| 15 mM | 0.1785 mL | 0.8926 mL | 1.7852 mL | 4.4630 mL | |
| 20 mM | 0.1339 mL | 0.6695 mL | 1.3389 mL | 3.3473 mL | |
| 25 mM | 0.1071 mL | 0.5356 mL | 1.0711 mL | 2.6778 mL |
AZD2716 関連分類
HY-120078 関連分類
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