Perspective: KAT6A inhibitors move from tool compounds to Phase III
- This perspective (a review, not primary research) outlines how lysine acetyltransferase inhibitors for cancer have advanced from tool compounds to many clinical candidates.
- It covers KAT6A structural biology and structure-activity relationships of acylsulfonylhydrazide, [1,2,4]thiadiazine and benzisoxazole sulfonamide inhibitors.
- Prifetrastat (PF-07248144), the most advanced KAT6A inhibitor, entered Phase III in 2025; the article also reviews trial updates, clinical challenges and opportunities.
💡 Points
Three unrelated chemotypes converging on one MYST-family acetyltransferase is the interesting part: acylsulfonylhydrazides, thiadiazines and benzisoxazole sulfonamides plausibly all sit in the acetyl-CoA site, so selectivity over the other MYST members is the real SAR battleground, not potency. Prifetrastat reaching Phase III suggests this polar, sulfonamide-heavy space can be made drug-like.
A KATing Edge Perspective on KAT6A Inhibitors as Anticancer Agents ↗