Transient Receptor Potential Melastatin 7 (TRPM7) Ion Channel Inhibitors: Preliminary SAR and Conformational Studies of Xenicane Diterpenoids from the Hawaiian Soft Coral .

Waixenicin A, a xenicane diterpene from the octocoral , is a selective, potent inhibitor of the TRPM7 ion channel. To study the structure-activity relationship (SAR) of waixenicin A, we isolated and assayed related diterpenes from . In addition to known waixenicins A () and B (), we purified six xenicane diterpenes, 7,8-epoxywaixenicins A () and B (), 12-deacetylwaixenicin A (), waixenicin E (), waixenicin F (), and 20-acetoxyxeniafaraunol B ().

Development and optimization of a high-throughput bioassay for TRPM7 ion channel inhibitors.

TRPM7 is a ubiquitously expressed and constitutively active divalent cation channel essential for cell survival and proliferation because it provides a mechanism for Mg2+ entry. This makes the channel an attractive target for proliferative diseases. In keeping with its role in Mg2+ homeostasis, TRPM7 is inhibited by intracellular Mg2+ and Mg-ATP.