We are currently investigating chemical biology of several highly bioactive natural products. In the case of bistramide A, also known as bistratene A, our laboratory established for the first time the correct mode of action of this important natural product by demonstrating that the previously proposed activity of this compound based on its ability to activate PKCd was incorrect. Our laboratory identified actin as the specific cellular receptor of bistramide A. This work was enabled by a series of biological an biochemical studies combined with the construction of a fully synthetic bistramide A-based affinity matrix and isolation of bistramide A-binding proteins in the cell lysate. This activity provides the molecular basis of the potent antiproliferative effects of bistramide A, identifying it as a valuable biochemical tool for studies of actin cytoskeleton, and a promising new lead for the development of a new class of antitumor agents.