A new group of potent inducers of differentiation in murine erythroleukemia cells

Proc Natl Acad Sci U S A. 1976 Mar;73(3):862-6. doi: 10.1073/pnas.73.3.862.

Abstract

This report identifies a group of compounds, polymethylene bisacetamides (acetylated diamines), which are potent inducers of erythroid differentiation in murine erythroleukemia cells. A known inducing agent, N-methylacetamide, was dimerized through varying numbers of methylenes in an attempt to increase the local effective concentration at adjacent target sites. The simple dimer was no more effective than N-methylacetamide alone; introduction of five to eight methylenes between acetamide groups substantially increased the effectiveness of these compounds. The hexamethylene bisacetamide was active between 0.5 mM and 5 mM; the percentage of cells induced and the rate at which they were recruited to differentiation was dependent upon the concentration of inducer within this range. At 5 mM hexamethylene bisacetamide essentially the entire population (greater than 99%) was induced to a pathway of erythroid differentiation which was greater differentiation of the cultured cells than with any inducer yet tested.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetamides / pharmacology*
  • Benzidines / metabolism
  • Cell Differentiation / drug effects*
  • Cell Line
  • Dimethyl Sulfoxide / pharmacology
  • Hemoglobins / biosynthesis
  • Leukemia, Erythroblastic, Acute / metabolism
  • Leukemia, Erythroblastic, Acute / pathology*
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Benzidines
  • Hemoglobins
  • Dimethyl Sulfoxide