Feeling its OATs

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. ...