Journal: Nature Communications

Article Title: A phenopushing platform to identify compounds that alleviate acute hypoxic stress by fast-tracking cellular adaptation

doi: 10.1038/s41467-025-57754-1

Figure Lengend Snippet: a Overview of AH-to-CH phenopushing screening and hit-calling framework. N: Normoxia. AH: Acute hypoxia (1 d). CH: Chronic hypoxia (6 d). D: Distance from the phenotypic profile of a perturbation (a given compound at a given dose) to the centroid of the phenotypic profiles of CH DMSO controls. θ : Angle of deviation from the phenotypic profile of a perturbation relative to the centroid of the phenotypic profiles of CH DMSO controls. The cell icons: Created in BioRender. Wu, A. (2025) https://BioRender.com/q85j552 . b Summary of geometric hit calls in the primary screen. Scatter plot and density map for distance (x-axis) and direction (y-axis) of bioactive compounds. Red solid line and dotted line show cutoffs for distance and angle, respectively. Vehicle (DMSO) controls in N, AH, and CH are shown for reference. Bioactive non-hit compounds (black dots), hits (red dots), and four hit examples (large red dots) are shown. c Screening funnel for AH-to-CH phenopushing hits. d Representative images for DMSO under N, AH, or CH compared to hit examples (highlighted in b) in AH (Temsirolimus, Deforolimus, KU-0063794, WYE-354). The experiment was independently repeated three times with similar results. Source data are provided as a Source Data file.

Article Snippet: Screened compounds included (1) Selleck FDA-approved & Passed Phase I Drug Library (L3800), (2) Selleck Kinase Inhibitor Library (L1200), (3) Selleck Apoptosis Compound Library (L3300), (4) Selleck Epigenetics Compound Library (L1900), (5) Selleck Bioactive Library (L1700), (6) manually curated FDA-approved & Passed Phase I drugs from other vendors, and (7) manually curated bioactive compounds from other vendors.

Techniques:

Journal: Nature Communications

Article Title: A phenopushing platform to identify compounds that alleviate acute hypoxic stress by fast-tracking cellular adaptation

doi: 10.1038/s41467-025-57754-1

Figure Lengend Snippet: a Overview of the ischemia rescue assay. The cell icons: Created in BioRender. Wu, A. (2025) https://BioRender.com/q85j552 . b Scatter plot of hit compound effects on HepG2 survival in ischemia-like stress. Cell survival: normalized to DMSO-treated cells, averaged across all tested well replicates and doses for each drug, and ranked based on their survival rate. Dashed lines: survival of DMSO-treated hypoxia naïve cells (bottom) or DMSO-treated cells pre-exposed to hypoxia for 6 days (top). mTOR/PI3Ki: AH-to-CH phenopushing hits targeting mTOR and/or PI3Ks. BETi: AH-to-CH phenopushing hits targeting BET proteins. Other: AH-to-CH phenopushing hits other than mTOR/PI3Ki and BET proteins. c Normalized cell survival of each tested dose for the top 25 hits shown in b . d Ischemia rescue effect comparison between the most effective tested dose of phenopushing (red) and non-phenopushing, bioactive (blue) compounds. Kernel density estimation used to smooth histograms. Dashed lines: (grey) mean survival of DMSO-treated cells or (red) 3x DMSO survival. Source data are provided as a Source Data file.

Article Snippet: Screened compounds included (1) Selleck FDA-approved & Passed Phase I Drug Library (L3800), (2) Selleck Kinase Inhibitor Library (L1200), (3) Selleck Apoptosis Compound Library (L3300), (4) Selleck Epigenetics Compound Library (L1900), (5) Selleck Bioactive Library (L1700), (6) manually curated FDA-approved & Passed Phase I drugs from other vendors, and (7) manually curated bioactive compounds from other vendors.

Techniques: Rescue Assay, Comparison