LDDRD has established an active network of collaborations aimed at structure-activity investigations and lead optimization research within selected series of novel antitumor and anti-HIV natural products. The goal is to introduce into the NCI drug development program improved members of known chemical and/or mechanistic classes currently under development and of continuing interest, as well as to introduce the best representatives of entirely new active chemical and/or mechanistic classes for consideration for entry into the drug development program. Subjects of current chemical and biological investigations include halichondrin-related compounds, e.g. halistatin, dolastatins, cephalostatins, cribrostatins, spongistatins, michellamines and related dimeric naphthylisoquinoline alkaloids and derivatives, korupensamines and related monomeric naphthylisoquinoline alkaloids and derivatives, calanolide derivatives and related compounds, ellipticines, ellipticiniums and related agents.