filgotinib (MedChemExpress)
Structured Review
![<t>Filgotinib</t> shows better efficacy in colon vs ileum precision-cut intestinal slices (PCIS) from Crohn’s disease (CD) patients in regulating critical type 1 and 17 related responses. Colon or ileum CD-derived PCIS were incubated for 24 h either unstimulated (Med) or stimulated using 10 μg/mL Concanavalin A combined with 100 nM filgotinib (ConA + Filg) or 0.05% DMSO vehicle control (ConA + Veh). Viability, absolute secretion of several mediators in supernatant, and gene expression analyses were performed. (A) Schematic representation (created with BioRender.com). (B) LDH release in supernatant normalized to lactate dehydrogenase (LDH) release of Triton X-100 lysed control tissue slices. (C) Absolute release of IL-17F, IL-21, IL-22, TRAIL, and CXCL10 levels in supernatant. N = 4 colon and N = 5 ileum donors. * P < .05, ** P < .01, *** P < .001, and **** P < .0001 by two-way ANOVA with Sidak’s multiple comparison test comparing ConA + vehicle vs ConA + filgotinib or ileum vs colon. (D) Volcano plot highlighting differential expression of genes in CD-derived PCIS comparing ConA + filgotinib vs ConA + vehicle in colon and ileum with highlighted genes for selected cytokines. It shows selected mediator-associated genes corresponding to the protein mediators highlighted in (C). This targeted analysis was used to assess whether the stronger mediator-level suppression observed in colonic PCIS was reflected at the mRNA level. The complete list of differentially expressed genes (DEGs) is provided in . Blue: enriched genes in ileum, red: enriched genes in colon, grey: no significant genes (DEGs; adj. P < .05, |log 2 [FC] | ≤ −1 for colon or ≥ 1 for ileum). (E) Correlation plots between log 2 fold changes in mRNA expression and corresponding cytokine secretion in ileum (blue) or colon (red).](https://pub-med-central-images-cdn.bioz.com/pub_med_central_ids_ending_with_3239/pmc13423239/pmc13423239__jjag101f3.jpg)
Filgotinib, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 95/100, based on 38 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/filgotinib/Filgotinib/pmc13423239-48-4-6
Average 95 stars, based on 38 article reviews
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1) Product Images from "Region-specific immune regulation determines differential response to JAK1 inhibition in Crohn’s disease ex vivo"
Article Title: Region-specific immune regulation determines differential response to JAK1 inhibition in Crohn’s disease ex vivo
Journal: Journal of Crohn's & Colitis
doi: 10.1093/ecco-jcc/jjag101
Figure Legend Snippet: Filgotinib shows better efficacy in colon vs ileum precision-cut intestinal slices (PCIS) from Crohn’s disease (CD) patients in regulating critical type 1 and 17 related responses. Colon or ileum CD-derived PCIS were incubated for 24 h either unstimulated (Med) or stimulated using 10 μg/mL Concanavalin A combined with 100 nM filgotinib (ConA + Filg) or 0.05% DMSO vehicle control (ConA + Veh). Viability, absolute secretion of several mediators in supernatant, and gene expression analyses were performed. (A) Schematic representation (created with BioRender.com). (B) LDH release in supernatant normalized to lactate dehydrogenase (LDH) release of Triton X-100 lysed control tissue slices. (C) Absolute release of IL-17F, IL-21, IL-22, TRAIL, and CXCL10 levels in supernatant. N = 4 colon and N = 5 ileum donors. * P < .05, ** P < .01, *** P < .001, and **** P < .0001 by two-way ANOVA with Sidak’s multiple comparison test comparing ConA + vehicle vs ConA + filgotinib or ileum vs colon. (D) Volcano plot highlighting differential expression of genes in CD-derived PCIS comparing ConA + filgotinib vs ConA + vehicle in colon and ileum with highlighted genes for selected cytokines. It shows selected mediator-associated genes corresponding to the protein mediators highlighted in (C). This targeted analysis was used to assess whether the stronger mediator-level suppression observed in colonic PCIS was reflected at the mRNA level. The complete list of differentially expressed genes (DEGs) is provided in . Blue: enriched genes in ileum, red: enriched genes in colon, grey: no significant genes (DEGs; adj. P < .05, |log 2 [FC] | ≤ −1 for colon or ≥ 1 for ileum). (E) Correlation plots between log 2 fold changes in mRNA expression and corresponding cytokine secretion in ileum (blue) or colon (red).
Techniques Used: Derivative Assay, Incubation, Control, Gene Expression, Comparison, Quantitative Proteomics, Expressing
Figure 5A . " title="Filgotinib modulates T cell-associated transcriptional programs in a region-specific ..." property="contentUrl" width="100%" height="100%"/>
Figure Legend Snippet: Filgotinib modulates T cell-associated transcriptional programs in a region-specific manner. Colon or ileum Crohn’s disease (CD)-derived precision-cut intestinal slices (PCIS) were incubated for 24 h either unstimulated (Med) or stimulated using 10 μg/mL Concanavalin A combined with 100 nM filgotinib (ConA + Filg) or 0.05% DMSO vehicle control (ConA + Veh). Upregulation of gene signature between PCIS from colon ( N = 3) and ileum ( N = 3) samples from CD patients was analyzed by mRNA sequencing. (A) Schematic representation of the treatment (created with BioRender.com). (B-C) Venn diagrams highlighting the overlap of all differential regulated genes (B; adj. P < .05) and all pathways (C), by comparing ConA + Veh and ConA + Filg in colon and ileum CD-derived PCIS. (D) Heatmap displaying expression levels of differentially expressed genes (DEGs; adj. P < .05, |log 2 [FC] | ≥ 1) among investigated groups. It shows the global transcriptome-level response to filgotinib and includes all DEGs identified after comparison of ConA + Filg vs ConA + Veh in ileal and/or colonic CD-derived PCIS according to the predefined statistical criteria. Genes are classified as shared, colon-specific or ileum-specific based on their significance in the respective regional comparison. The complete list of DEGs is provided in . Hierarchical clustering based on Euclidean distance. (E-F) Selected gene-level analysis of T cell receptor signaling and T cell subset-associated transcriptional programs for ConA + Veh vs ConA + Filg treated CD-derived PCIS from colon ( N = 3) or ileum ( N = 3). Genes were selected to illustrate immune programs identified within the broader filgotinib-regulated transcriptomic response. The corresponding pathway-level analysis is shown in
Techniques Used: Derivative Assay, Incubation, Control, Sequencing, Expressing, Comparison
Figure 4E and . Complete pathway enrichment results, including pathway names, database sources, contributing genes, P- values and FDR-adjusted P- values, are provided in . (B–D) Gene expression levels of selected genes for ConA + Veh- vs ConA + Filg-treated CD-derived PCIS from colon ( N = 3) or ileum ( N = 3). (E) ROS/RNS release in PCIS supernatants after stimulation. MFI was normalized to total protein content. (F) Release of nitrate and nitrite in PCIS supernatant after stimulation was added up to the total NO (NOx) and normalized to total protein content. N = 3 donors each. * P < .05 and ** P < .01 by two-way ANOVA with Sidak’s multiple comparison test comparing ConA + Veh vs Med, ConA + Veh vs ConA + Filg, or ileum vs colon. " title="Filgotinib preferentially suppresses immune activation and oxidative stress responses ..." property="contentUrl" width="100%" height="100%"/>
Figure Legend Snippet: Filgotinib preferentially suppresses immune activation and oxidative stress responses in the colon vs ileum. Colon or ileum Crohn’s disease (CD)-derived precision-cut intestinal slices (PCIS) were incubated for 24 h either unstimulated (Med) or stimulated using 10 μg/mL Concanavalin A combined with 100 nM filgotinib (ConA + Filg) or 0.05% DMSO vehicle control (ConA + Veh). Upregulation of gene signature by mRNA sequencing and reactive oxygen/nitrogen species (ROS/RNS) as well as nitrogen oxides (Nox) (sum of nitrate [NO 3 − ] and nitrite [NO 2 − ] release measurements were performed. Analysis between PCIS from colon ( N = 3) and ileum ( N = 3) samples from CD patients were performed. (A) Over-representation analysis of filgotinib-regulated gene sets in ConA-stimulated ileal (blue) and colonic (red) CD-derived PCIS. This pathway-level analysis provides the functional context for the selected T cell-associated gene-level changes shown in
Techniques Used: Activation Assay, Derivative Assay, Incubation, Control, Sequencing, Functional Assay, Gene Expression, Comparison
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