histone deacetylase inhibitor
Meaning of histone deacetylase inhibitor: A drug that leaves chemical tags in place on the spools DNA winds around, changing which genes a cell can reach.
Definition of histone deacetylase inhibitor
A histone deacetylase inhibitor is a drug that blocks the enzymes which strip acetyl tags from histones, the proteins DNA coils around. With the tags left in place the coil loosens, and genes that had been packed away become readable again. Several of these drugs are approved treatments for particular lymphomas and for myeloma, and many others have been tested in trials.
What do histones do?
A single human cell holds around two meters of DNA inside a nucleus too small to see. The DNA manages this by winding twice around clusters of eight histone proteins, like thread around a series of spools. Those spools coil into fibers and the fibers fold again. Packing solves the space problem but creates another: DNA wound tightly onto a spool cannot be read. Access has to be controlled, and the tags attached to the histones are the control.
How does acetylation act as a switch?
| State | Enzyme responsible | Effect on the coil |
|---|---|---|
| Acetyl tags attached | Histone acetyltransferase | Loosens; genes can be read |
| Tags removed | Histone deacetylase | Tightens; genes are silenced |
| Tags kept in place | Blocked by the inhibitor | Stays loose; silenced genes reopen |
Histones carry a positive charge and DNA a negative one, so the two attract. An acetyl tag neutralizes part of that positive charge, the grip weakens, and the DNA loosens from the spool. Removing the tag restores the grip.
What are they used for?
Vorinostat and romidepsin are approved for cutaneous T-cell lymphoma, romidepsin and belinostat for peripheral T-cell lymphoma, and panobinostat has been used with other drugs in myeloma. Why blood cancers respond and solid tumors largely have not is unresolved. Valproic acid, long used for seizures and mood, also inhibits these enzymes, a property discovered well after it entered use.
What effects do they have?
Because gene activity across the whole cell shifts, the effects are broad rather than narrow. Fatigue, nausea, diarrhea, low platelet counts and changes in the heart's electrical recovery time are the ones most consistently reported for the class. Calling an HDAC inhibitor a targeted drug describes the enzyme it binds, not the reach of what follows.
Also known as
Used in a sentence
A histone deacetylase inhibitor was selected following relapse of cutaneous T-cell lymphoma.
Good to know
Several of these drugs are approved treatments rather than experimental compounds, and their effects are broad because they shift gene activity across the whole cell.
Word origin
Where “histone deacetylase inhibitor” comes from
Histone comes from the Greek histos, meaning web or tissue, applied to these proteins when they were first isolated.