Docking simulation study and kinase selectivity of f152A1 and its analogs.

f152A1 is a potent inhibitor of MAP kinases and TNFα-transcription. When f152A1 and its analogs are assayed against ERK2, MEK1, and MEKK1, these compounds show different inhibition profiles. It is considered that the highly reactive cis-enone moiety and modifications of the 14-membered resorcylic lactone ring may determine their kinase selectivity and potency.

Conformational analyses and MO studies of f152A1 and its analogues as potent protein kinase inhibitors.

f152A1 was isolated from a fermentation broth of Curvularia verruculosa and characterized as a potent inhibitor of TNFalpha transcription, with anti-inflammatory activity. f152A1 and several analogues displayed inhibitory activity against the MAP kinases ERK2 and MEK1 in in vitro kinase assays. Through SAR studies on f152A1 and analogues prepared via total synthesis, we have identified structural features that contribute to inhibitory activity.