Fig. 4. Bioactivity of cabrillostatin (1) and cabrillospirals A (2) and B (3).

A Principal component analysis of high dimensional phenotypic profiles of 1–3 (red, green, yellow, respectively), reference compounds (gray), and DMSO (blue) in nine diverse cell lines: AsPC 1 (human pancreas), A549 (lung), DU145 (prostate), HCT116 (colon), HEPG2 (hepatoma), OVCAR4 (ovarian), U87MG (glioblastoma), WM164 (melanoma), 786-O (renal). DMSO (dimethyl sulfoxide). B Bioactivity expressed as significance (−log² p val) across all cell lines. Responses above the dashed line are considered significant (p < 10⁻⁶). P values for compound-to-DMSO distances were calculated based on the empirical null distribution of DMSO-DMSO distances (one-sided, no adjustments for multiple comparisons; Methods). C Representative Ca²⁺ transient traces of DMSO (top) and 1 (bottom). D Scatter plot showing beating frequency and mean peak amplitude of 1 (red), DMSO (blue), and anti-arrhythmic and anti-cancer drugs (gray).