Strongylophorines: natural product inhibitors of hypoxia-inducible factor-1 transcriptional pathway.

Rapidly increasing experimental and clinical data provides evidence for the role of hypoxia inducible factor-1 (HIF-1) as a crucial mediator of tumor survival and progression. In our effort to identify inhibitors of the HIF-1 activation pathway, we screened fractions from marine invertebrates. Fractions from an extract of Petrosia (Strongylophora) strongylata potently inhibited the HIF-1 activation pathway. Strongylophorines 2, 3, and 8 isolated from the active fractions were found to be responsible for the HIF-1 inhibition with EC 50 values of 8, 13, and 6 microM, respectively.