L'Universel : l'Évangile c'est la liberté ! / direction H. Huchet

mai 19041904/05 (N13)-1904/05.Appartient à l’ensemble documentaire : HNormand

BioMAP activity profile of compound 4.

<p>Black thin arrow indicates cytotoxicity at 1 μM in the 3C system. The 3C system was excluded from further analysis at this concentration (indicated by horizontal bracket). Grey arrows indicate anti-proliferative activity. Abbreviations (full details in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189247#sec002" target="_blank">Materials & methods</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189247#pone.0189247.s002" target="_blank">S2 Table</a>): 3C and 4H (HuVEC, venular endothelial cells), LPS and SAg (PBMC, peripheral blood mononuclear cells + HuVEC), BT (B cells + PBMC), BE3C (NHBE, normal human bronchial epithelial cells), BF4T (NHBE + NHDF, normal human dermal fibroblasts), HDF3CGF (NHDF), KF3CT (NHK, normal human keratinocytes + NHDF), CASM3C (CASMC, coronary artery smooth muscle cells), MyoF (HLF, human lung fibroblasts) and /Mphg (HuVEC, M1 macrophages).</p

Inhibition of TSLP production by mTOR inhibitors everolimus and AZD8055.

<p>Inhibition of TSLP production by mTOR inhibitors everolimus and AZD8055.</p

Main pharmacological activities identified in compound 4.

<p>Main pharmacological activities identified in compound 4.</p

Production of TSLP in NHBE cells from the 2 donors used in this study.

<p>Production of TSLP in NHBE cells from the 2 donors used in this study.</p

Quality control of primary phenotypic screen.

<p>(A) Z’ factor versus plate number. (B) Global representation of total and basal activity values for all plates.</p

List of selected hit compounds.

<p>For TSLP protein and mRNA determinations results were obtained using NHBE cells from donor #1. Results are shown as geometric mean IC₅₀ (μM) (95% confidence interval) or average % inhibition ± SD at the indicated concentration [μM]. Specific activities evaluated are indicated in each case and shown in bold. Activities reported in ^a [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189247#pone.0189247.ref044" target="_blank">44</a>], ^b [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189247#pone.0189247.ref045" target="_blank">45</a>], ^c [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189247#pone.0189247.ref046" target="_blank">46</a>], ^d [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189247#pone.0189247.ref047" target="_blank">47</a>] and ^e [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189247#pone.0189247.ref032" target="_blank">32</a>].</p

Correlation between inhibition of TSLP production and biochemical and cellular kinase activities of reference compound 7 (p38 inhibitor) and tofacitinib (JAK inhibitor).

<p>For TSLP protein determinations, results were obtained using NHBE cells from donor #1. Results are shown as geometric mean IC₅₀ (μM) (95% confidence interval) or average % inhibition ± SD at the indicated concentration [μM]. Specific activities evaluated are indicated in each case and shown in bold.</p

Active compounds identified in the hit expansion exercise.

<p>Results obtained using NHBE cells from donor #1 in the TSLP assay. Results shown as geometric mean IC₅₀, μM (95% confidence interval) or average % inhibition ± SD at the indicated concentration. Biochemical and cell based specific activities evaluated are indicated in each case and shown in bold.</p

Summary of final conditions used for the phenotypic assay.

<p>Summary of final conditions used for the phenotypic assay.</p