APLIDINE (Aplidin®, Dehydrodidemnin B)

Source: The tunicate Aplidium albicans (CHORDATA)
Activity: Anti-cancer agent via apoptosis induction
Status: Phase II clinical trials

Aplidine (Dehydrodidemnin B), has was isolated from the Mediterranean tunicate Aplidium albicans. It was first reported in a 1991 patent application. In preclinical animal tests, Aplidine exhibited marked anticancer properties, outperforming the related compound didemnin B by a factor of six.

Aplidine differs chemically from didemnin B and the other didemnins only in the structure of its side chain. This fact, along with the small size and relatively simple structure, has allowed research to achieve total synthesis of didemnin analogs. Synthesis has permitted the replacing of some amino acids non-essential for bioactivity with covalent bonds, which has increased resistance to enzymatic degradation and prolonged the bioactive lifetime. Analogs more active than any of the original natural didemnins have been produced in this manner.

The molecule has been described as a multifactorial apoptosis inducer, and it has other beneficial attributes such as low toxicity and a high specificity for tumor cells. The varied inferred mechanisms of action thus far reported include rapid and persistent activation of apoptosis and interruption of the tumor cell cycle at the G1-G2. The compound also inhibits the expression of receptor proteins (ornithine descarboxylase) and the secretion of proteins (vascular endothelial growth factor) involved in growth and vascularization of certain tumor types.

Synthetically derived Aplidine, under the PharmaMar trade name Aplidin®, is currently in Phase II trials for a variety of cancers, including melanoma, colorectal, renal, lung, head and neck (non-cerebral), pancreatic and medullary thyroid carcinomas. Additional Phase II trials against other forms of cancer are commencing. Aplidin was granted "orphan drug status" in the EU for acute lymphoblastic leukemia in 2003.

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Amador, M.L., Jimeno, J., Paz-Ares, L., Cortes-Funes, H., and M. Hidalgo. 2003. Progress in the development and acquisition of anticancer agents from marine sources. Annals of Oncology 14:1607-1615.

Kijjoa A and P Sawangwong. 2004. Drugs and cosmetics from the sea (review paper). Mar. Drugs 2004:73-82.

Newman DJ, and GM Cragg. 2004. Advanced preclinical and clinical trials of natural products and related compounds from marine sources. Current Medicinal Chemistry 11:1693-1713.