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Chemical Structure| 448906-42-1 Chemical Structure| 448906-42-1

Structure of ITE
CAS No.: 448906-42-1

Chemical Structure| 448906-42-1

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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.

Keywords: AhR ligand ; Endothelial cells ; Sexual dimorphism ; Transcriptome ; Phosphoproteome

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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.

Keywords: AhR ligand ; placentas ; preeclampsia ; sexual dimorphism ; trans_x005f_x0002_criptomics ; vasculature

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Product Details of ITE

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

Safety of ITE

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

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 <<

Protocol

Bio Calculators
Preparing Stock Solutions 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

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