Structure of ITE
CAS No.: 448906-42-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
ITE is an AhR agonist with Ki value of 3nM, and also inhibits TGF-β-induced human myofibroblast differentiation.
Synonyms: ITE
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Zhao, Ying-jie ; Zhang, Si-yan ; Wei, Ying-ying ; Li, Hui-hui ; Lei, Wei ; Wang, Kai , et al.
Abstract: We have reported that an endogenous aryl hydrocarbon receptor (AhR) ligand, 2-(1’H-indole-3’-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), inhibits functions of human umbilical vein endothelial cells (HUVECs) and induces preeclampsia (PE)-like symptoms in rats. Herein, we tested the hypothesis that ITE impairs endothelial functions via disturbing transcriptome and phosphoproteome in HUVECs. We measured AhR activity in human maternal and umbilical vein sera from PE and normotensive (NT) pregnancies. The serum-induced changes in CYP1A1/B1 mRNA (indexes of AhR activation) in HUVECs were quantified using RT-qPCR. ITE’s effects on endothelial proliferation and monolayer integrity in female and male HUVECs were determined. We profiled ITE-induced changes in transcriptome and phosphoproteome in HUVECs using RNA-seq and bottom-up phosphoproteomics, respectively. After 12 hr of treatment, umbilical vein sera from PE increased CYP1A1 mRNA (1.7-fold of NT) in HUVECs, which was blocked by CH223191, an AhR antagonist. ITE dose-dependently inhibited endothelial proliferation (76%-87% of control) and time-dependently reduced endothelial integrity with a maximum inhibition (~ 10%) at 40 hr. ITE induced 140 and 80 differentially expressed genes in female and male HUVECs, respectively. ITE altered phosphorylation of 92 and 105 proteins at 4 and 24 hr, respectively, in HUVECs. These ITE-dysregulated genes and phosphoproteins were enriched in biological functions and pathways that are relevant to heart, liver, and kidney diseases, vascular functions, and inflammatory responses. Thus, endogenous AhR ligands may impair endothelial functions by disturbing transcriptome and phosphoproteome. These AhR ligand-dysregulated genes and phosphoproteins may be therapeutic and cell sex-specific targets for PE-induced endothelial dysfunction.
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Keywords: AhR ligand ; Endothelial cells ; Sexual dimorphism ; Transcriptome ; Phosphoproteome
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An endogenous aryl hydrocarbon receptor ligand induces preeclampsia-like phenotypes in rats
Zhao, Ying‐Jie ; Zhou, Chi ; Zhang, Si‐Yan ; Mishra, Jay S ; Li, Hui‐Hui ; Lei, Wei , et al.
Abstract: Preeclampsia (PE) is a hypertensive disorder during human pregnancy. Aryl hydro-carbon receptor (AhR) is a ligand-activated transcription factor. Exogenous and endogenous AhR ligands can induce hypertension in male rats and mice. Herein, using rats as a model, we tested the hypothesis that over-regulation of endogenous AhR ligands during pregnancy impairs vascular functions by disrupting the transcriptome in the placenta, contributing to the development of PE. Pregnant rats were injected daily with an endogenous AhR ligand, 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), from gestational day (GD) 10 to 19. Maternal mean blood pressure was measured on GD16–20. Proteinuria and uteroplacental blood flow were monitored on GD20. Placentas collected on GD20 were used to determine changes in vascular density and transcriptome. Compared with the vehicle control, ITE elevated maternal mean blood pressure by 22% and 16% on GD16 and 17, respectively. ITE increased proteinuria by 50% and decreased uteroplacental blood flow by 26%. ITE reduced the placental vascular density by 18%. RNA sequencing analysis revealed that ITE induced 1316 and 2020 differentially expressed genes (DEGs) in female and male placentas, respectively. These DEGs were enriched in pathways relevant to heart diseases, vascular functions and inflammation. Bioinformatics analysis also predicted that ITE altered immune cell infiltration in placentas depending on fetal sex. These data suggest that over-regulation of endogenous AhR ligands may lead to PE with impaired vascular functions and disrupted fetal sex-specific transcriptomes and immune cell infiltration in placentas. These AhR ligand-induced DEGs and pathways may represent promising therapeutic targets for PE-induced cardiovascular dysfunctions.
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Keywords: AhR ligand ; placentas ; preeclampsia ; sexual dimorphism ; trans_x005f_x0002_criptomics ; vasculature
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CAS No. : | 448906-42-1 |
Formula : | C14H10N2O3S |
M.W : | 286.31 |
SMILES Code : | O=C(C1=CSC(C(C2=CNC3=C2C=CC=C3)=O)=N1)OC |
Synonyms : |
ITE
|
MDL No. : | MFCD06411597 |
InChI Key : | KDDXOGDIPZSCTM-UHFFFAOYSA-N |
Pubchem ID : | 4668801 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Clinical Trial:
NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
NCT00386100 | Diabetes Mellitus, Type 2 | Phase 4 | Completed | - | - |
NCT01243424 | Diabetes Mellitus, Type 2 | Phase 3 | Completed | - | - |
NCT03108768 | Hearing Loss, Bilateral Sensor... More >>ineural, Progressive Less << | Not Applicable | Completed | - | Switzerland ... More >> Sonova AG Stafa, Zürich, Switzerland, 8712 Less << |
NCT03569228 | Hearing Loss | Not Applicable | Not yet recruiting | October 29, 2022 | United States, Tennessee ... More >> Mountain Home VA Medical Center James H. Quillen VA Medical Center, Mountain Home, TN Not yet recruiting Mountain Home, Tennessee, United States, 37684 Contact: Sherri L Smith, PhD 423-926-1171 ext 7569 sherri.smith@va.gov Principal Investigator: Sherri L. Smith, PhD Less << |
NCT00386100 | - | Completed | - | - | |
NCT02545569 | Hearing Loss, Bilateral or Uni... More >>lateral Less << | Not Applicable | Not yet recruiting | December 2020 | Switzerland ... More >> Sonova AG Recruiting Staefa, Zürich, Switzerland, 8712 Contact: Jana-Kosima Schwarzlos 0041 58 928 0101 JanaKosima.Schwarzlos@sonova.com Less << |
NCT02709486 | Osteoarthritis, Hip ... More >> Osteoarthritis, Knee Less << | Phase 3 | Active, not recruiting | December 2018 | - |
NCT01619345 | Diabetes Heal... More >>thy Less << | Phase 1 | Completed | - | United Kingdom ... More >> Nottingham, United Kingdom, NG11 6JS Less << |
NCT02436629 | High Intensity Intermittent Sp... More >>orts Performance Less << | Phase 4 | Completed | - | Netherlands ... More >> Maastricht University Medical Centre+ Maastricht, Limburg, Netherlands, 6200MD Less << |
NCT01746992 | ALK-negative Anaplastic Large ... More >>Cell Lymphoma Peripherial T Cell Lymphoma,Not Otherwise Specified Angioimmunoblastic T Cell Lymphoma Enteropathy Associated T Cell Lymphoma Hepatosplenic T Cell Lymphoma Subcutaneous Panniculitis Like T Cell Lymphoma Less << | Phase 4 | Active, not recruiting | December 2018 | China, Shanghai ... More >> Ruijin hospital Shanghai, Shanghai, China, 200025 Less << |
NCT03596346 | Food Safety | Not Applicable | Completed | - | Finland ... More >> Satucon Oy/Pihlajalinna Ite Kuopio, Finland, 70100 Less << |
NCT03770754 | Necrosis | Not Applicable | Enrolling by invitation | January 20, 2019 | Mexico ... More >> Jorge Paredes Vieyra Tijuana, Baja California, Mexico, 22000 Jorge Paredes Vieyra Tijuana, Baja Califronia, Mexico, 22000 Jose Clemente Orozco Tijuana, BC, Mexico, 22000 Jose Clemente Tijuana, BC, Mexico, 22000 Less << |
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1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
3.49mL 0.70mL 0.35mL |
17.46mL 3.49mL 1.75mL |
34.93mL 6.99mL 3.49mL |
Tags: ITE | AhR | Metabolic Enzyme | 448906-42-1
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