Short-chain fatty acid-hexosamine cancer prodrugs: The sugar matters!

Srinivasa Gopalan Sampathkumar, Christopher T. Campbell, Christopher Weier, Kevin J. Yarema

Research output: Contribution to journalReview articlepeer-review

18 Scopus citations


This review describes short-chain fatty acid (SCFA)-sugar hybrids, exemplified by the lead compound But4ManNAc where n-butyrate is linked to N-acetyl-D-mannosamine (ManNAc) in a single molecule, that merge two emerging modes of cancer therapy. First, n-butyrate is a histone deacetylase (HDAC) inhibitor that remodels chromatin, thereby influencing patterns of gene expression to 'make bad cells go good'. Second, ManNAc is the dedicated precursor for sialic acid biosynthesis, a sugar that is gaining increasing recognition as an important modulator of cell fate, including apoptosis, proliferation and differentiation. Herein we describe how, when combined with n-butyrate, ManNAc augments the epigenetic activity of the HDAC inhibitor to achieve sugar-dependent killing of cancer cells in vitro. Looking forward to the translation of this class of compounds into the clinic, we then discuss how the poor pharmacological properties of the individual n-butyrate and ManNAc moieties are dramatically improved by combination in a single molecule, where they function as mutual prodrugs. Finally, we conclude by outlining how But 4ManNAc represents a versatile platform for future drug development efforts.

Original languageEnglish (US)
Pages (from-to)1099-1116
Number of pages18
JournalDrugs of the Future
Issue number12
StatePublished - 2006
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


Dive into the research topics of 'Short-chain fatty acid-hexosamine cancer prodrugs: The sugar matters!'. Together they form a unique fingerprint.

Cite this