Published on
Monday, February 12, 2007
Conventional antimitotic agents work by binding tubulin. But a pair of papers
published last week in The Proceedings of the National Academy of Sciences
showed that diazonamide A, the parent compound of Joyant Pharmaceuticals Inc.’s
AB-5, arrests the cell cycle by binding to ornithine aminotransferase (OAT),
an enzyme known to be involved in amino acid catabolism and gluconeogenesis,
but never previously implicated in the cell cycle.
While the first paper explained how diazonamide A works, the second showed
that Joyant’s AB-5 - a synthetic analog of the toxin - could arrest tumor growth
in xenograft mouse models while avoiding the side effects common in tubulin-binding
antimitotics such as weight loss and neutropenia