Bisubstrate analogue structure-activity relationships for p300 histone acetyltransferase inhibitors

Vatsala Sagar, Weiping Zheng, Paul R. Thompson, Philip A. Cole

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3383-3390
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume12
Issue number12
DOIs
StatePublished - Jun 15 2004

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Histone Acetyltransferases
Coenzyme A
Structure-Activity Relationship
Lead compounds
Solid-Phase Synthesis Techniques
Gene expression
Neoplasms
Derivatives
Gene Expression
Enzymes
Pharmaceutical Preparations
p300-CBP-associated factor
Therapeutics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Bisubstrate analogue structure-activity relationships for p300 histone acetyltransferase inhibitors. / Sagar, Vatsala; Zheng, Weiping; Thompson, Paul R.; Cole, Philip A.

In: Bioorganic and Medicinal Chemistry, Vol. 12, No. 12, 15.06.2004, p. 3383-3390.

Research output: Contribution to journalArticle

Sagar, Vatsala ; Zheng, Weiping ; Thompson, Paul R. ; Cole, Philip A. / Bisubstrate analogue structure-activity relationships for p300 histone acetyltransferase inhibitors. In: Bioorganic and Medicinal Chemistry. 2004 ; Vol. 12, No. 12. pp. 3383-3390.
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