Mar.Drugs 2014,12 1075 the microorganisms area.However,despite the large number of NCEs isolated from marine organisms many of them with pronounced biological activity,the great majority does not surpass the pharmaceutical pre-clinical trials and only a very few have been marketed as pharmaceutical products. Besides the usual drawbacks in any drug discovery process,the industrial development of many promising MNP was hampered by additional difficulties such as sustainable source and issues related to structural complexity and scale up.Nevertheless,the global marine pharmaceutical pipeline remains very active and includes,at the moment,eight Food and Drug Admnistration(FDA)or European Medicines Agency (EMEA)approved drugs and several compounds in different phases of the clinical pipeline [67].From the eight compounds currently on the market (Figure 1),only three (Prialt while the rest of them suffered lead optimization,in different steps of their development.Overall,from lead discovery to the entry in the market it took 20 to 30 years.Ensuring natural product supply on an industrial scale.optimization of formulation and ADMET properties were the main blockades faced by pharmaceutical companies.Optimization of NP by structural modifications,synthetic supply of unmodified natural molecule or immunoconjugation of NP was the strategy behind these successful stories.The history of the development of the market drugs will be discussed in this subsection with a focus on the approaches tackled by the pharmaceutical companies that succeeded in marketing their products Figure 1.Chemical structures of marine drugs on the market divided by therapeutic area. Cance N-C ypertriglyceridemiMar. Drugs 2014, 12 1075 the microorganisms area. However, despite the large number of NCEs isolated from marine organisms, many of them with pronounced biological activity, the great majority does not surpass the pharmaceutical pre-clinical trials and only a very few have been marketed as pharmaceutical products. Besides the usual drawbacks in any drug discovery process, the industrial development of many promising MNP was hampered by additional difficulties such as sustainable source and issues related to structural complexity and scale up. Nevertheless, the global marine pharmaceutical pipeline remains very active and includes, at the moment, eight Food and Drug Admnistration (FDA) or European Medicines Agency (EMEA) approved drugs and several compounds in different phases of the clinical pipeline [67]. From the eight compounds currently on the market (Figure 1), only three (Prialt® , Yondelis® and Carragelose® ), became drugs without any modification of the original natural molecule, while the rest of them suffered lead optimization, in different steps of their development. Overall, from lead discovery to the entry in the market it took 20 to 30 years. Ensuring natural product supply on an industrial scale, optimization of formulation and ADMET properties were the main blockades faced by pharmaceutical companies. Optimization of NP by structural modifications, synthetic supply of unmodified natural molecule or immunoconjugation of NP was the strategy behind these successful stories. The history of the development of the market drugs will be discussed in this subsection with a focus on the approaches tackled by the pharmaceutical companies that succeeded in marketing their products. Figure 1. Chemical structures of marine drugs on the market divided by therapeutic area