Journal: Frontiers in Pharmacology

Article Title: Integrating text mining with network models for successful target identification: in vitro validation in MASH-induced liver fibrosis

doi: 10.3389/fphar.2024.1442752

Figure Lengend Snippet: Visualization of a growth factor to the extracellular matrix (GF–ECM) pathway. (A) Pathway from GF (TFGB1) to ECM protein (COL1A2). (B) Alternative route of the GF–ECM pathway when EP300 is knocked out.

Article Snippet: The HSCs were incubated for 4 days in STECM supplemented with 1% (v/v) FBS and 1% (v/v) antibiotic solution with or without TGF-β1 (2 ng/mL) and TGF-β1 cotreated with the TGFβ type I receptor kinase (ALK5) inhibitor LY-364947 or one of the EP300 inhibitors L002 or inobrodib (CCS1477) (all from MedChemExpress).

Techniques:

Journal: Frontiers in Pharmacology

Article Title: Integrating text mining with network models for successful target identification: in vitro validation in MASH-induced liver fibrosis

doi: 10.3389/fphar.2024.1442752

Figure Lengend Snippet: Highlighted results of the EP300 quick scan. In the quick scan, databases ( Supplementary Material S1.3 ) were queried for evidence that support the role of the candidate drug target (EP300) in liver fibrosis. Top-ranked candidate targets were subjected to an in-depth target efficacy assessment by domain experts ( Table 3 ).

Article Snippet: The HSCs were incubated for 4 days in STECM supplemented with 1% (v/v) FBS and 1% (v/v) antibiotic solution with or without TGF-β1 (2 ng/mL) and TGF-β1 cotreated with the TGFβ type I receptor kinase (ALK5) inhibitor LY-364947 or one of the EP300 inhibitors L002 or inobrodib (CCS1477) (all from MedChemExpress).

Techniques: Knockdown, Activation Assay, Inhibition, Microarray, Comparison, Expressing, In Vitro, In Vivo, Ex Vivo, Over Expression, Activity Assay, Binding Assay, Knock-Out

Journal: Frontiers in Pharmacology

Article Title: Integrating text mining with network models for successful target identification: in vitro validation in MASH-induced liver fibrosis

doi: 10.3389/fphar.2024.1442752

Figure Lengend Snippet: Evidence in support of the roles of EP300 in MASH-related fibrosis obtained by expert-based in-depth target efficacy assessment. The key findings derived from literature and other data sources are shown. The full EP300 efficacy assessment is available in Supplementary Material S2 .

Article Snippet: The HSCs were incubated for 4 days in STECM supplemented with 1% (v/v) FBS and 1% (v/v) antibiotic solution with or without TGF-β1 (2 ng/mL) and TGF-β1 cotreated with the TGFβ type I receptor kinase (ALK5) inhibitor LY-364947 or one of the EP300 inhibitors L002 or inobrodib (CCS1477) (all from MedChemExpress).

Techniques: Derivative Assay, Functional Assay, Expressing, Activation Assay, Injection, Mutagenesis, Knock-Out, Control, Transgenic Assay, Dominant Negative Mutation, shRNA, Binding Assay, Inhibition, In Vitro, In Vivo

Journal: Frontiers in Pharmacology

Article Title: Integrating text mining with network models for successful target identification: in vitro validation in MASH-induced liver fibrosis

doi: 10.3389/fphar.2024.1442752

Figure Lengend Snippet: Genetic structure of EP300 with its functional domains and exemplified interaction partners. CH, cysteine-/histidine-rich domain; KIX, kinase inhibitory domain, Br, bromodomain. Adapted from .

Article Snippet: The HSCs were incubated for 4 days in STECM supplemented with 1% (v/v) FBS and 1% (v/v) antibiotic solution with or without TGF-β1 (2 ng/mL) and TGF-β1 cotreated with the TGFβ type I receptor kinase (ALK5) inhibitor LY-364947 or one of the EP300 inhibitors L002 or inobrodib (CCS1477) (all from MedChemExpress).

Techniques: Functional Assay

Journal: Frontiers in Pharmacology

Article Title: Integrating text mining with network models for successful target identification: in vitro validation in MASH-induced liver fibrosis

doi: 10.3389/fphar.2024.1442752

Figure Lengend Snippet: Silencing RNA (siRNA) targeting EP300 shows a significant ( p -value < 0.05) reduction in fibrosis. Total collagen levels measured in primary hepatic stellate cells (HSCs) in the presence of siRNA targeting either eGFP (blue, control siRNA) or EP300 (yellow). Aside from the untreated controls, the cells were stimulated with TGFβ (+TGFβ) in the absence or presence of the ALK5 inhibitor (+TGFβ+Alk5-i). The data are presented as mean ± SD (n = 3).

Article Snippet: The HSCs were incubated for 4 days in STECM supplemented with 1% (v/v) FBS and 1% (v/v) antibiotic solution with or without TGF-β1 (2 ng/mL) and TGF-β1 cotreated with the TGFβ type I receptor kinase (ALK5) inhibitor LY-364947 or one of the EP300 inhibitors L002 or inobrodib (CCS1477) (all from MedChemExpress).

Techniques: Control

Journal: Frontiers in Pharmacology

Article Title: Integrating text mining with network models for successful target identification: in vitro validation in MASH-induced liver fibrosis

doi: 10.3389/fphar.2024.1442752

Figure Lengend Snippet: Intervention studies with small-molecule inhibitors of EP300 (inobrodib and L002) as a case study for target validation. (A) Inobrodib (Ino) and L002 significantly decrease TGFβ-induced fibrosis in LX-2 cells. The total collagen levels for treatment with Ino, L002, and ALK5 inhibitor (Alk5-i) are shown after TGFβ stimulation compared to the non-stimulated control. (B) Corresponding total protein levels. (C) Ino, L002, and Alk5-i, decreased TGFβ-induced fibrosis in primary HSCs. The total collagen levels for treatment with Ino, L002, and Alk5-i are shown after TGFβ stimulation compared to the non-stimulated control. (D) Corresponding total protein levels. The data are presented as mean ± SD (n ≥ 3). Significance ( p < 0.05) is indicated with respect to the TGFβ-stimulated control (*) or Alk5-i (#).

Article Snippet: The HSCs were incubated for 4 days in STECM supplemented with 1% (v/v) FBS and 1% (v/v) antibiotic solution with or without TGF-β1 (2 ng/mL) and TGF-β1 cotreated with the TGFβ type I receptor kinase (ALK5) inhibitor LY-364947 or one of the EP300 inhibitors L002 or inobrodib (CCS1477) (all from MedChemExpress).

Techniques: Control