Bisubstrate analogue structure-activity relationships for p300 histone acetyltransferase inhibitors

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology



Document Type


Medical Subject Headings

Acetyltransferases; Cell Cycle Proteins; Coenzyme A; Enzyme Inhibitors; Histone Acetyltransferases; Lysine; Molecular Structure; Structure-Activity Relationship; Transcription Factors; p300-CBP Transcription Factors


Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics


p300 and CBP are important histone acetyltransferases (HATs) that regulate gene expression and may be anti-cancer drug targets. Based on a previous lead compound, Lys-CoA, we have used solid phase synthesis to generate a series of 11 new analogues and evaluated these compounds as HAT inhibitors. Increased spacing between the CoA moiety and the lysyl moiety generally decreases inhibitory potency. We have found two substituted derivatives that show about 4-fold increased potency compared to the parent compound Lys-CoA. These structure-activity studies allow for a greater understanding of the optimal requirements for potent inhibition of HAT enzymes and pave the way for a novel class of anti-cancer therapeutics.

Rights and Permissions

Citation: Bioorg Med Chem. 2004 Jun 15;12(12):3383-90. Link to article on publisher's site


At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed