The relative distance from the PLS-DA scores plot between treatment and sham-operated group urine samples in ESI mode.

<p>^a scutellarin</p><p>^b nimodipine</p><p>^c scutellarein; compared to the model group</p><p>*<i>p</i> < 0.05</p><p>**<i>p</i> < 0.01</p><p>The relative distance from the PLS-DA scores plot between treatment and sham-operated group urine samples in ESI mode.</p

Biochemical indicator levels in hippocampal tissue.

<p>For statistical analysis: <i>vs</i> sham-operated group</p><p>^△<i>p</i> < 0.05</p><p>^△△<i>p</i> < 0.01; <i>vs</i> model group</p><p>*<i>p</i> < 0.05</p><p>**<i>p</i> < 0.01.</p><p>Biochemical indicator levels in hippocampal tissue.</p

Plasma PCA score plot (A), S-plot of OPLS-DA data (B), hippocampal tissue PCA score plot (C), and S-plot of OPLS-DA data between the sham-operated and model groups in negative mode (D).

<p>C, sham-operated group, M, model group.</p

PLS-DA analytical results from urine samples of BCCAO rats treated with Scu (A) or Scue (B) at six therapeutic cycles in positive mode.

<p>C, sham-operated group (0–12 h); M, model group (0–12 h); Scu 1–6, after administration of Scu for 0–12 h (Scu1), 12–24 h (Scu2), 24–36 h (Scu3), 36–48 h (Scu4), 48h-60 h (Scu5) and 60–72 h (Scu6); Scue 1–6, after administration of Scue for 0–12 h (Scue1), 12–24 h (Scue2), 24–36 h (Scue3), 36–48 h (Scue4), 48h-60 h (Scue5) and 60–72 h (Scue6). <b>PLS-DA analytical results from BCCAO rat urine samples treated with Scu, Scue, and nimodipine at 12–24 h in positive (C) and negative modes (D).</b> C, sham-operated group; M, model group; Scu, after administration of Scu; Scue, after administration of Scue; N, after administration of nimodipine.</p

UPLC-MS identification of potential biomarkers.

<p>^a urine metabolite</p><p>^b brain metabolite</p><p>^c plasma metabolite.</p><p>UPLC-MS identification of potential biomarkers.</p

Correlative analysis of biomarkers and biochemical data in hippocampal tissue.

<p>^a brain metabolite</p><p>*<i>p</i> < 0.05</p><p>**<i>p</i> < 0.01</p><p>Correlative analysis of biomarkers and biochemical data in hippocampal tissue.</p

Metabolomics pathway analysis (MetPA) summary.

<p>(A) Urine, a) sphingolipid metabolism and b) lysine biosynthesis; (B) hippocampal tissue, a) alanine, aspartate, and glutamate metabolism; and (C) Plasma, a) sphingolipid metabolism.</p

Discovery of RORγ Allosteric Fluorescent Probes and Their Application: Fluorescence Polarization, Screening, and Bioimaging

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function

Discovery of RORγ Allosteric Fluorescent Probes and Their Application: Fluorescence Polarization, Screening, and Bioimaging

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function

Discovery of RORγ Allosteric Fluorescent Probes and Their Application: Fluorescence Polarization, Screening, and Bioimaging

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function