Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE125446 | GEO | 2019/01/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor.

Project description:The transcription factor nuclear factor of activated T cells (NFAT) has a key role in both T cell activation and tolerance and has emerged as an important target of immune modulation. NFAT directs the effector arm of the immune response in the presence of activator protein-1 (AP-1), and T cell anergy/exhaustion in the absence of AP-1. Envisioning a strategy for selective modulation of the immune response, we designed a FRET-based high-throughput screen to identify compounds that disrupt the NFAT:AP-1:DNA complex. We screened ?202,000 small organic compounds and identified 337 candidate inhibitors. We focus here on one compound, N-(3-acetamidophenyl)-2-[5-(1H-benzimidazol-2-yl)pyridin-2-yl]sulfanylacetamide (Compound 10), which disrupts the NFAT:AP-1 interaction at the composite antigen-receptor response element-2 site without affecting the binding of NFAT or AP-1 alone to DNA. Compound 10 binds to DNA in a sequence-selective manner and inhibits the transcription of the Il2 gene and several other cyclosporin A-sensitive cytokine genes important for the effector immune response. This study provides proof-of-concept that small molecules can inhibit the assembly of specific DNA-protein complexes, and opens a potential new approach to treat human diseases where known transcription factors are deregulated.

| S-EPMC6525529 | biostudies-literature

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor I

Project description:The transcription factor NFAT has a key role in both T cell activation and tolerance and has emerged as an important target of immune modulation. NFAT directs the effector arm of the immune response in the presence of AP-1, and T cell anergy/exhaustion in the absence of AP-1. Envisioning a strategy for selective modulation of the immune response, we designed a FRET-based high-throughput screen to identify compounds that disrupt the NFAT:AP-1:DNA complex. We screened ~202,000 small organic compounds and identified 337 candidate inhibitors. We focus here on one compound, N-(3-acetamidophenyl)-2-[5-(1H-benzimidazol-2-yl)pyridin-2-yl]sulfanylacetamide (Compound 10), which disrupts the NFAT:AP-1 interaction at the composite ARRE-2 site without affecting the binding of NFAT or AP-1 alone to DNA. Compound 10 binds to DNA in a sequence-selective manner and inhibits the transcription of the Il2 gene and several other CsA-sensitive cytokine genes important for the effector immune response. This study provides proof-of-concept that small molecules can inhibit the assembly of specific DNA-protein complexes, and opens a potential new approach to treat human diseases where known transcription factors are deregulated.

2019-01-23 | GSE125443 | GEO

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor III

2019-01-23 | GSE125445 | GEO

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor II

2019-01-23 | GSE125444 | GEO

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor

Project description:Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor

| PRJNA516414 | ENA

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor I

Project description:Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor I

| PRJNA516417 | ENA

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor III

Project description:Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor III

| PRJNA516418 | ENA

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor II

Project description:Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor II

| PRJNA516419 | ENA

Targeting of the NOTCH transcription complex by a novel small molecule inhibitor CB-103

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-12-19 | GSE142408 | GEO

Small molecule inhibitors targeting activator protein 1 (AP-1).

Project description:Activator protein 1 (AP-1) is a pivotal transcription factor that regulates a wide range of cellular processes including proliferation, apoptosis, differentiation, survival, cell migration, and transformation. Accumulating evidence supports that AP-1 plays an important role in several severe disorders including cancer, fibrosis, and organ injury, as well as inflammatory disorders such as asthma, psoriasis, and rheumatoid arthritis. AP-1 has emerged as an actively pursued drug discovery target over the past decade. Excitingly, a selective AP-1 inhibitor T-5224 (51) has been investigated in phase II human clinical trials. Nevertheless, no effective AP-1 inhibitors have yet been approved for clinical use. Despite significant advances achieved in understanding AP-1 biology and function, as well as the identification of small molecules modulating AP-1 associated signaling pathways, medicinal chemistry efforts remain an urgent need to yield selective and efficacious AP-1 inhibitors as a viable therapeutic strategy for human diseases.

| S-EPMC4148154 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data