SH-11037
SH-11037 is a potent inhibitor of soluble epoxide hydrolase (sEH) and docks to the substrate binding cleft in the sEH hydrolase domain. SH-11037 dose-dependently suppresses angiogenesis in the choroidal sprouting assay ex vivo and inhibited ocular developmental angiogenesis in zebrafish larvae. SH-11037 reduces choroidal neovascularisation lesion volume in the laser-induced CNV mouse model. SH-11037 synergises with anti-VEGF treatments in vitro and in vivo. SH-11037 induces G2/M phase blockade and retains retinal endothelial cell viability at active concentrations without overt toxicity. SH-11037 can be used for the research of retinal neovascularization and ocular neovascularization.
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- CAS 番号: 1638153-78-2
- 分子式: C34H39NO10
- 分子量:621.67
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
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sEH |
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Cell Line
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Type | Value | Description | References |
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| ARPE-19 | GI50 |
100 μM
Compound: SH-11037
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Cytotoxicity against human ARPE-19 cells assessed as cell growth inhibition incubated for 44 hrs by AlamarBlue reagent based fluorescence assay
Cytotoxicity against human ARPE-19 cells assessed as cell growth inhibition incubated for 44 hrs by AlamarBlue reagent based fluorescence assay
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[PMID: 36938984] |
SH-11037 (14a) potently and selectively inhibits the proliferation of human microvascular retinal endothelial cells (HRECs) with a GI50 of 0.055 μM, showing ~14-fold selectivity over HUVECs, >1000-fold selectivity over 92-1 cells, and ~218-fold selectivity over Y79 cells[1].
SH-11037 dose-dependently inhibits human microvascular retinal endothelial cell (HREC) proliferation without inducing apoptotic nuclear changes[1].
SH-11037 (30-600 nM) dose-dependently inhibits the migration of human microvascular retinal endothelial cells (HRECs) in a scratch wound assay, with significant inhibition observed at concentrations ≥300 nM[1].
SH-11037 (30-500 nM) dose-dependently inhibits the tube formation of human microvascular retinal endothelial cells (HRECs) on Matrigel, with significant inhibition observed at concentrations ≥100 nM[1].
SH-11037 (50-600 nM) induces minimal apoptosis in human microvascular retinal endothelial cells (HRECs), with <10% of cells undergoing apoptosis at concentrations up to 600 nM[1].
SH-11037 (30-1000 nM) does not reduce the viability of human microvascular retinal endothelial cells (HRECs)[1].
SH-11037 (100-1000 nM; 48 h) causes a dose-dependent G2/M phase cell cycle arrest in human microvascular retinal endothelial cells (HRECs) without significant induction of apoptosis[1].
SH-11037 (1 μM; up to 2 h) is stable in pH 7.4 phosphate buffer but undergoes rapid, quantitative enzymatic hydrolysis to SH-11008 in mouse plasma (half-life 0.018 min) and slower hydrolysis in dog (half-life 69.1 min) and human plasma (half-life 73.2 min)[2].
SH-11037 (1 μM; up to 2 h) has carboxylesterase as the predominant enzyme mediating rapid hydrolysis to SH-11008 in mouse plasma and mouse eye homogenate; paraoxonase 1 and butyrylcholinesterase mediate slower hydrolysis in dog plasma, while only paraoxonase 1 mediates hydrolysis in human plasma[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human microvascular retinal endothelial cells
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Concentration:100 nM; 300 nM; 1000 nM
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Incubation Time:48 h
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Result:Arrested HRECs at the G2/M phase of the cell cycle.
SH-11037 (1-10 μM) inhibits ocular angiogenesis in zebrafish larvae[4].
SH-11037 (0.1-100 μM; i.v.; single dose) has no toxic effects to eye[4].
SH-11037 (0.1-10 μM; i.v.; single dose) dose-dependently suppresses choroidal neovascularisation (CNV) lesion volume[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR (male, 8 weeks old, 30~35 g)[2]
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Dosage:5 mg/kg
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Administration:i.v.; single dose
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Result:Exhibited plasma levels below quantitation limit (<0.24 ng/mL) throughout 24-hour time course.
Produced hydrolytic metabolite with peak concentration (Cmax) of 738.1 ng/mL at 5 minutes, area under the curve (AUCinf) of 14,728.5 ng·min/mL, and half-life (t1/2) of 3.6 minutes, detected above quantitation limit up to 30 minutes.
Reached fraction converted to fm of 102.7%.
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Animal Model:ICR (male, 8 weeks old, 30~35 g)[2]
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Dosage:10 mg/kg
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Administration:p.o.; single dose
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Result:Showed plasma levels below quantitation limit throughout 24-hour time course.
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Animal Model:C57BL/6J (female, 6-8 weeks)[4]
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Dosage:0.1 μM; 1 μM; 10 μM; 100 μM
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Administration:i.v.; single dose
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Result:Showed no histological changes in retinal sections.
Showed no morphological changes to retinal thickness.
Showed no signs of retinal injury, apoptosis or inflammation.
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Animal Model:C57BL/6J (female, 6-8 weeks)[4]
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Dosage:0.1 μM; 0.3 μM; 1 μM; 10 μM
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Administration:i.v.; single dose
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Result:Reduced CNV lesion size at 1 and 10 μM compared to vehicle controls.
Reduced leakiness of CNV lesions relative to the vehicle treatment.
化学情報
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CAS 番号 1638153-78-2
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分子量 621.67
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分子式 C34H39NO10
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SMILES
COC1=C2C(OCC(C2=O)CC3=CC(OC([C@@H](NC(OC(C)(C)C)=O)CC4=CC=CC=C4)=O)=C(C=C3)OC)=CC(OC)=C1OC
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
[1]. Basavarajappa HD, et al. Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization. J Med Chem. 2015;58(12):5015-5027. [Content Brief]
[2]. Kim EY, et al. Mouse Pharmacokinetics and In Vitro Metabolism of SH-11037 and SH-11008, Synthetic Homoisoflavonoids for Retinal Neovascularization. Pharmaceutics. 2022;14(11):2270. Published 2022 Oct 24. [Content Brief]
[3]. Sulaiman RS, et al. Chemical Proteomics Reveals Soluble Epoxide Hydrolase as a Therapeutic Target for Ocular Neovascularization. ACS Chem Biol. 2018 Jan 19;13(1):45-52. [Content Brief]
[4]. Sulaiman RS, et al. A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy. Sci Rep. 2016 May 5;6:25509. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
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