Metabolites2012.2 314 Administration(FDA)approved drugs,one EU registered drug,13 natural products (or derivatives thereof)in different phases of the clinical pipeline and a large number of marine chemicals in the pre-clinical pipeline [78].Some examples include,Ziconotide (Prialt,Elan Corporation)a peptide first discovered in a tropical cone snail,which was approved in December 2004 for the treatment of pain Plitidepsin (34)(Aplidin,PharmaMa),a depsipeptide was isolated from the Mediterranean tunicate Aplidium albicans [79,80].Plitidepsin(34)is effective in treating various cancers,including melanoma,small cell and non-small cell lung.bladder as well as non-Hodgkin lymphoma and acute lymphoblastic leukemia and is currently in Phase II clinical trials (Figure 11)[78.81].Ecteinascidin 743 (ET743:YondelisTM)(35)was isolated in very low vields from the ascidian Ecteinascidia turbinata [82,83].The quantities of ET743(35)required for advanced pre-clinical and clinical studies was achieved by adopting very large-scale aquaculture of E.turbinata in open ponds,however the semisynthesis of ET743 (35)has been well established (Figure 11)[81,84,85].In October 2007 Trabectedin (35)(also known as Ecteinascidin 743 or ET-743)(Yondelis.PharmaMar)became the first marine anticancer drug to be approved in the European Union [78].Trabectedin (35)has been approved by the European Agency for the Evaluation of Medicinal Products (EMEA)and is completing key Phase III studies in the US for approval [78].Spisulosine (36),isolated from the marine clam Spisua polynyma,exhibited substantial selective activity against tumor cells compared to normal cells [86].It advanced to Phase I clinical trials against solid tumors but was withdrawn in late 2006 [87-89].Cryptophycin (37)was selected for clinical trials in the mid 1990s then advanced to phase II trials but was terminated in 2002 due to toxicity and lack of efficacy (Figure 11)[90] Figure 11.Plitidepsin(34).ET743,Spisulosine(36)and Cryptophycin(37) OH OMetabolites 2012, 2 314 Administration (FDA) approved drugs, one EU registered drug, 13 natural products (or derivatives thereof) in different phases of the clinical pipeline and a large number of marine chemicals in the pre-clinical pipeline [78]. Some examples include, Ziconotide (Prialt®, Elan Corporation) a peptide first discovered in a tropical cone snail, which was approved in December 2004 for the treatment of pain. Plitidepsin (34) (Aplidin®, PharmaMa), a depsipeptide was isolated from the Mediterranean tunicate Aplidium albicans [79,80]. Plitidepsin (34) is effective in treating various cancers, including melanoma, small cell and non-small cell lung, bladder as well as non-Hodgkin lymphoma and acute lymphoblastic leukemia and is currently in Phase II clinical trials (Figure 11) [78,81]. Ecteinascidin 743 (ET743; Yondelis™) (35) was isolated in very low yields from the ascidian Ecteinascidia turbinata [82,83]. The quantities of ET743 (35) required for advanced pre-clinical and clinical studies was achieved by adopting very large-scale aquaculture of E. turbinata in open ponds, however the semisynthesis of ET743 (35) has been well established (Figure 11) [81,84,85]. In October 2007, Trabectedin (35) (also known as Ecteinascidin 743 or ET-743) (Yondelis, PharmaMar) became the first marine anticancer drug to be approved in the European Union [78]. Trabectedin (35) has been approved by the European Agency for the Evaluation of Medicinal Products (EMEA) and is completing key Phase III studies in the US for approval [78]. Spisulosine (36), isolated from the marine clam Spisula polynyma, exhibited substantial selective activity against tumor cells compared to normal cells [86]. It advanced to Phase I clinical trials against solid tumors but was withdrawn in late 2006 [87–89]. Cryptophycin (37) was selected for clinical trials in the mid 1990s then advanced to phase II trials but was terminated in 2002 due to toxicity and lack of efficacy (Figure 11) [90]. Figure 11. Plitidepsin (34), ET743, Spisulosine (36) and Cryptophycin (37)