A new microtubule-binding molecule, myoseverin, was identified from a libra
ry of 2,6,9-trisubstituted purines in a morphological differentiation scree
n. Myoseverin induces the reversible fission of multinucleated myotubes int
o mononucleated fragments. Myotube fission promotes DNA synthesis and cell
proliferation after removal of the compound and transfer of the cells to fr
esh growth medium. Transcriptional profiling and biochemical analysis indic
ate that myoseverin alone does not reverse the biochemical differentiation
process. Instead, myoseverin affects the expression of a variety of growth
factor, immunomodulatory, extracellular matrix-remodeling, and stress respo
nse genes, consistent with the activation of pathways involved in wound hee
ling and tissue regeneration.