Elevenostat is a multi-HDAC inhibitor biased to HDAC6, not an HDAC11-selective probe
- Re-testing Elevenostat (JB3-22) against recombinant HDAC isoforms with two orthogonal HDAC11 assays showed only weak HDAC11 inhibition.
- Full HDAC1–11 profiling found much stronger inhibition of HDAC6 and HDAC10, plus class I enzymes, with HDAC11 the least sensitive isoform.
- Cellular readouts (tubulin and histone acetylation, reduced viability) matched HDAC6 and class I engagement, so past HDAC11 conclusions drawn from this compound need re-reading.
💡 Points
This is the unglamorous but valuable kind of paper: a compound used as an HDAC11 tool turns out to hit HDAC6 hardest. Any phenotype published with Elevenostat now has an attribution problem. Before I reuse an inhibitor as a probe, I want full-panel selectivity and a matched inactive control, which this case argues for.