Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ATI-1777 a topical JAK1/3 inhibitor may benefit atopic dermatitis without systemic drug exposure, results from preclinical development and Phase 2a randomized-control study ATI-1777-AD-201

ABSTRACT: ATI-1777 a topical JAK1/3 inhibitor may benefit atopic dermatitis without systemic drug exposure, results from preclinical development and Phase 2a randomized-control study ATI-1777-AD-201

PROVIDER: PRJNA1021651 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR26197666_1.fastq.gz	Fastqsanger.gz
	SRR26197666_2.fastq.gz	Fastqsanger.gz
	SRR26197667_1.fastq.gz	Fastqsanger.gz
	SRR26197667_2.fastq.gz	Fastqsanger.gz
	SRR26197668_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 30

Similar Datasets

ATI-1777 a topical JAK1/3 inhibitor may benefit atopic dermatitis without systemic drug exposure, results from preclinical development and Phase 2a randomized-control study ATI-1777-AD-201

Project description:Atopic dermatitis (AD), a chronic, pruritic skin disease, affects 10%-30% of children and up to 14% of adults in developed countries. Since current AD treatments may lead to systemic drug exposure and AD pathophysiology is partially mediated by JAK1/3 signaling, ATI-1777, a potent and selective JAK1/3 inhibitor, was designed with multiple sites of metabolism to deliver local efficacy in the skin and limit systemic exposure. In preclinical studies, ATI-1777 selectively inhibited JAK1/3 with limited systemic exposure and without any adverse effects. ATI-1777-AD-201 (NCT04598269), a Phase 2a, first-in-human, randomized, double-blind,vehicle-controlled, parallel-group study, evaluated the efficacy, safety, tolerability, and pharmacokinetics of ATI-1777 topical solution in 48participants with AD over 4 weeks. The primary outcome was reduction of a modified EASI score from baseline; reduction was significantly greater in the ATI-1777 group at Day28 compared to vehicle (percent reduction from baseline 74.45% [SE6.455] and 41.43% [SE6.189], respectively [p<0.001]). Average plasma concentrations of ATI-1777 were <5% of the IC50 of ATI-1777 for inhibiting JAK1/3. No deaths or serious adverse events were reported. This demonstrates that topical ATI-1777 does not lead to pharmacologically relevant systemic drug exposure and may reduce clinical signs of AD.

2023-11-20 | GSE244201 | GEO

ATI-1777, a Topical Jak1/3 Inhibitor, May Benefit Atopic Dermatitis without Systemic Drug Exposure: Results from Preclinical Development and Phase 2a Randomized Control Study ATI-1777-AD-201.

Project description:IntroductionAtopic dermatitis, a chronic, pruritic skin disease, affects 10-30% of children and up to 14% of adults in developed countries. ATI-1777, a potent and selective Jak1/3 inhibitor, was designed with multiple sites of metabolism to deliver local efficacy in the skin and limit systemic exposure. In preclinical studies, ATI-1777 selectively inhibited Jak1/3 with limited systemic exposure and without any adverse effects.Primary objectiveThe primary goal of this study was to assess the preliminary clinical efficacy of ATI-1777 topical solution in adults with moderate or severe atopic dermatitis.DesignATI-1777-AD-201, a phase 2a, first-in-human, randomized, double-blind, vehicle-controlled, parallel-group study, evaluated the efficacy, safety, tolerability, and pharmacokinetics of ATI-1777 topical solution in 48 participants with atopic dermatitis over 4 weeks.Primary endpointThe primary endpoint was a reduction of a modified Eczema Area and Severity Index score from baseline.ResultsReduction was significantly greater in the ATI-1777-treated group on day 28 than in vehicle-treated group (percentage reduction from baseline = 74.45% [standard error = 6.455] and 41.43% [standard error = 6.189], respectively [P < .001]). Average plasma concentrations of ATI-1777 were <5% of the half-maximal inhibitory concentration of ATI-1777 for inhibiting Jak1/3. No deaths or serious adverse events were reported.ConclusionTopical ATI-1777 does not lead to pharmacologically relevant systemic drug exposure and may reduce clinical signs of atopic dermatitis.Trial registrationThe study was registered at ClinicalTrials.gov with the number NCT04598269.

| S-EPMC10825549 | biostudies-literature

Transcription profiling of human JAK1 wild-type and JAK1 mutation-positive T cell acute lymphoblastic leukemia blasts

Project description:Aberrant signal transduction contributes substantially to leukemogenesis. The Janus kinase 1 (JAK1) gene encodes a cytoplasmic tyrosine kinase that noncovalently associates with a variety of cytokine receptors and plays a nonredundant role in lymphoid cell precursor proliferation, survival, and differentiation. Somatic mutations in JAK1 occur in individuals with acute lymphoblastic leukemia (ALL). JAK1 mutations were more prevalent among adult subjects with the T cell precursor ALL, where they accounted for 18% of cases, and were associated with advanced age at diagnosis, poor response to therapy, and overall prognosis; We used microarray to compare the gene expression profile of JAK1 mutation positive or negative ALL blasts Experiment Overall Design: Thawed or freshly isolated T-ALL cells (>90% blasts) were homogenized, total RNA was extracted and hybridized on Affymetrix microarrays

2009-10-02 | E-GEOD-18239 | biostudies-arrayexpress

4SC-201 (Resminostat) in Advanced Colorectal Carcinoma

Project description:The purpose of this study is to determine the Maximum Tolerated Dose (MTD) of 4SC-201 (Resminostat) in combination with FOLFIRI and whether 4SC-201 (Resminostat) is effective and safe in combination FOLFIRI versus FOLFIRI alone in the treatment of advanced colorectal carcinoma.

| 2100868 | ecrin-mdr-crc

Sinorhizobium meliloti strain:201

Project description:Sinorhizobium meliloti 201 Resequencing

| PRJNA501490 | ENA

Selective inhibitors of JAK1 targeting a subtype-restricted allosteric cysteine

Project description:The JAK family of non-receptor tyrosine kinases includes four subtypes (JAK1, JAK2, JAK3, and TYK2) and is responsible for signal transduction downstream of diverse cytokine receptors. JAK inhibitors have emerged as important therapies for immuno(onc)ological disorders, but their use is limited by undesirable side effects presumed to arise from poor subtype selectivity, a common challenge for inhibitors targeting the ATP-binding pocket of kinases. Here, we describe the chemical proteomic discovery of a druggable allosteric cysteine present in the non-catalytic pseudokinase domain of JAK1 (C817) and TYK2 (C838), but absent from JAK2 or JAK3. Electrophilic compounds selectively engaging this site block JAK1-dependent transphosphorylation and cytokine signaling, while appearing to act largely as “silent” ligands for TYK2. Importantly, the allosteric JAK1 inhibitors do not impair JAK2-dependent cytokine signaling and are inactive in cells expressing a C817A JAK1 mutant. Our findings thus reveal an allosteric approach for inhibiting JAK1 with unprecedented subtype selectivity.

2023-07-20 | PXD031384 | Pride

Expression data from JAK1 wild-type and JAK1 mutation-positive T cell acute lymphoblastic leukemia blasts

Project description:Aberrant signal transduction contributes substantially to leukemogenesis. The Janus kinase 1 (JAK1) gene encodes a cytoplasmic tyrosine kinase that noncovalently associates with a variety of cytokine receptors and plays a nonredundant role in lymphoid cell precursor proliferation, survival, and differentiation. Somatic mutations in JAK1 occur in individuals with acute lymphoblastic leukemia (ALL). JAK1 mutations were more prevalent among adult subjects with the T cell precursor ALL, where they accounted for 18% of cases, and were associated with advanced age at diagnosis, poor response to therapy, and overall prognosis We used microarray to compare the gene expression profile of JAK1 mutation positive or negative ALL blasts

2009-09-24 | GSE18239 | GEO

Asticcacaulis sp. 201

Project description:Asticcacaulis sp. 201 Genome sequencing and assembly

| PRJNA1009033 | ENA

Effect of JAK1/3 blockade on IL2 response in NK cells

Project description:IL2 signals are transmitted through JAK1 and JAK3, but the transcriptomic consequences of each to the overall response is unclear. Here we analyzed the relative contribution of JAK1 and JAK3 to the NK cell IL2 response in vitro using titrated doses of isoform specific JAK inhibitors. Blockade of JAK1 and JAK3 have unequal effects on IL2-induced transcripts at pharmacologically relevant doses. Splenic NK cells were isolated by negative selection from 6wk old male C57BL/6 mice. These were cultured with IL2 (250U/ml) in the presence or absence of JAK1/3 inhibitors for 8hrs in vitro. Cells were then transferred directly into TriZol. RNA was prepared in Trizol for gene expression profiling by Affymetrix Mouse Gene 1.0 ST Arrays.

2016-07-20 | E-GEOD-84562 | biostudies-arrayexpress

Gene expression profiling upon knockdown of JAK1 in IM9 cells

Project description:Natural Killer (NK) cells are primary effectors of innate immunity directed against transformed cells. In response, tumor cells have developed mechanisms to evade NK cell-mediated lysis but the molecular basis for target cell resistance is not well understood. In the present study, we used a lentiviral shRNA library targeting more than 1000 human genes to identify 83 genes that promote target cell resistance to human NK cells. Many of the genes identified in this genetic screen belong to common signaling pathways, however, none of these genes have previously been known to modulate susceptibility of human tumor cells to immunologic destruction. In particular, gene silencing of two members of the JAK family (JAK1 and JAK2) in a variety of tumor cell targets increased their susceptibility to NK-mediated lysis and induced increased secretion of interferon gamma (IFN-gamma by NK cells. Treatment of tumor cells with JAK inhibitors also induced increased susceptibility to NK cell activity. These findings may have important clinical implications and suggest that small molecule inhibitors of tyrosine kinases being developed as therapeutic anti-tumor agents may also have significant immunologic effects in vivo. IM9 cells were transduced with shRNA-encoding vectors and selected with Puromycin. Two vectors were specifically targeting JAK1 (JAK1-1 and JAK1-3) and one vector encoded an irrelevant control shRNA (CTRL-2). Total RNA was obtained from the parental IM9 cell line, the control-shRNA expressing IM9 cells, the JAK1-1-shRNA and JAK1-3-shRNA expressing IM9 cells in 2 separate experiments (Exp1 and Exp2).

2012-06-27 | E-GEOD-37012 | biostudies-arrayexpress

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