Drugs from the Oceans: Marine Natural Products as Leads for Drug Discovery.

The marine environment harbors a vast number of species that are the source of a wide array of structurally diverse bioactive secondary metabolites. At this point in time, roughly 27'000 marine natural products are known, of which eight are (were) at the origin of seven marketed drugs, mostly for the treatment of cancer. The majority of these drugs and also of drug candidates currently undergoing clinical evaluation (excluding antibody-drug conjugates) are unmodified natural products, but synthetic chemistry has played a central role in the discovery and/or development of all but one of the approved marine-derived drugs. More than 1000 new marine natural products have been isolated per year over the last decade, but the pool of new and unique structures is far from exhausted. To fully leverage the potential offered by the structural diversity of marine-produced secondary metabolites for drug discovery will require their broad assessment for different bioactivities and the productive interplay between new fermentation technologies, synthetic organic chemistry, and medicinal chemistry, in order to secure compound supply and enable lead optimization.