Journal: Toxicological Sciences

Article Title: Nonclinical safety assessment of SBT777101, a CAR-engineered regulatory T cell therapy for autoimmune diseases

doi: 10.1093/toxsci/kfag125

Figure Lengend Snippet: SBT777101 demonstrates minimal antigen-specific activation without impact on normal human cell survival. (A) Representative flow cytometry plots showing surface (top) and intracellular (bottom) binding of SBT777101 scFv-Fc (right) relative to isotype control (left) in SNU449 cells. (B) In vitro functional characterization using SNU449 cells ± CV-beads. Left: Mean ± SD CD69 expression (only SBT777101 data shown; no activation observed in UT controls). Data analyzed by two-way ANOVA with Sidak’s multiple comparisons test. Right: Cytotoxicity measured as the number of viable target cells remaining, normalized to no-Treg controls. Data analyzed by one-way ANOVA with Tukey’s multiple comparisons test. (C) Percentage of UT (top) or SBT777101 (bottom) Tregs expressing CD69 after 24-h co-culture with normal human primary cells or CV-beads (positive control). Data represent mean ± SD from three replicates. Independent experiments are separated by dashed vertical lines. Comparisons were made for media alone compared with in the presence of primary cells for each type and analyzed by two-tailed unpaired t -test. (D) Cytotoxicity (mean ± SD) of SBT777101 and UT Tregs against the same primary cell panel, normalized to no-Treg controls. Data analyzed by one-way ANOVA with Tukey’s multiple comparisons test. (E) Fold-change in CD71 expression (mean ± SD; relative to media control) across three donors after 72-h culture with media, CitP − SKNBE2 cells, CitP + SNU449 cells, human brain astrocytes (HBA), or CV-beads. CV beads were prepared in RPMI or AGM media as appropriate. Full lysis controls (B, D) represent target cells treated with Triton X-100. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001. All experiments included 3 technical replicates. AGM, astrocyte growth medium; CitP, citrullinated protein; CV, citrullinated vimentin; HMEC, human mammary epithelial cells; NHBE, normal human bronchial epithelial cells; NHDF, normal human dermal fibroblasts; PrEC, prostate epithelial cells; RPTEC, renal proximal tubule epithelial cells; scFv, single-chain variable fragment; UT, untransduced.

Article Snippet: Primary human cells (mammary epithelial cells [HMEC; Lonza Cat#CC-2551], normal bronchial epithelial cells [NHBE; Lonza Cat#CC2451], renal proximal tubule epithelial cells [RPTEC; Lonza Cat#CC2553], prostate epithelial cells [PrEC; Lonza Cat#CC2555], hepatocytes [Lonza Cat#HUCPG], brain astrocytes [HBA; Neuromics Cat#HMP202], iPSC-derived myocytes [Tempo Bioscience Cat#1014], iPSC-derived cortical neurons [Tempo Bioscience Cat#201], and monocyte-derived macrophages [internally derived]) and the positive-control SNU449 cell line (ATCC Cat#CRL-2234) were assessed for binding of the SBT777101 scFv by flow cytometry.

Techniques: Activation Assay, Flow Cytometry, Binding Assay, Control, In Vitro, Functional Assay, Expressing, Co-culture Assay, Positive Control, Two Tailed Test, Lysis

Journal: bioRxiv

Article Title: Overcoming the accuracy–generalization tradeoff in docking and scoring for prospective virtual screening

doi: 10.64898/2026.08.03.742480

Figure Lengend Snippet: Clusters of IL17A experimentally validated hits.

Article Snippet: LY3509754 (MedChemExpress, HY-139206) was used as a positive-control IL17A inhibitor.

Techniques:

Journal: bioRxiv

Article Title: Overcoming the accuracy–generalization tradeoff in docking and scoring for prospective virtual screening

doi: 10.64898/2026.08.03.742480

Figure Lengend Snippet: Prospective virtual screening campaigns were conducted against four therapeutically relevant targets representing distinct target classes and binding-site architectures. CD73 (nucleotidase), IRAK4 (kinase), and Factor XI (FXIa protease) were targeted through orthosteric inhibition, whereas IL-17A, a protein–protein interaction (PPI) target, was targeted through an allosteric binding site. For each target, the experimentally determined hit rate, a representative validated hit, its biochemical potency ( IC 50), and its structural similarity to the closest previously reported inhibitor (ECFP4 Tanimoto coefficient) are shown. The prospective campaigns identified 56 active compounds from 183 tested for CD73, 19 from 127 for IRAK4, 13 from 299 for Factor XI, and 6 from 194 for IL-17A. Across all four targets, representative hits exhibited low structural similarity to known inhibitors (ECFP4 Tanimoto coefficients of 0.22–0.27), demonstrating the ability of the virtual screening workflow to prospectively identify chemically novel scaffolds across both conventional orthosteric targets and more challenging protein–protein interaction targets.

Article Snippet: Zimlovisertib (MedChemExpress, HY-19836) was used as a positive-control IRAK4 inhibitor.

Techniques: Binding Assay, Inhibition

Journal: bioRxiv

Article Title: Overcoming the accuracy–generalization tradeoff in docking and scoring for prospective virtual screening

doi: 10.64898/2026.08.03.742480

Figure Lengend Snippet: (a) Prospective virtual screening workflow. Approximately 80 billion compounds from Enamine REAL Space were computationally screened and progressively prioritized to 153 compounds for procurement, of which 127 were experimentally evaluated. The number of compounds remaining after each filtering stage and the corresponding biochemical and cellular hit rates are shown. (b) Characterization of validated hits. Top, single-concentration biochemical inhibition measured at 100 and 10 μM . Middle, molecular weight (MW) and topological polar surface area (TPSA) distributions of validated hits. Bottom left, UMAP projection of ECFP4 fingerprints comparing validated hits (orange) with previously reported IRAK4 inhibitors (blue). Bottom right, distribution of ECFP4 Tanimoto similarity between validated hits and the closest known IRAK4 inhibitor, illustrating the chemical novelty of the identified compounds. (c) Representative validated IRAK4 inhibitors. Chemical structures, biochemical and cellular IC 50 values, physicochemical properties, and representative dose-response curves for two non-nucleotide inhibitors.

Article Snippet: Zimlovisertib (MedChemExpress, HY-19836) was used as a positive-control IRAK4 inhibitor.

Techniques: Concentration Assay, Inhibition, Molecular Weight