NEOVASTAT® (AE-941)

Source: Taxonomically identified shark species harvested under sustainable conditions (CHORDATA)
Activity: Anti-tumor agent; anti-angiogenic agent
Status: Preclinical

Neovastat (AE-941) is a derivative of shark cartilage extract. Rather than being a specific monomolecular compound, AE-941 is a defined standardized liquid extract comprising the < 500 kDa (kilodaltons, a unit of mass) fraction from shark cartilage.

The multiple mechanisms of action thus far reported for AE-941 are impressive. As a primary MOA, research suggests AE-941 inhibits the binding of Vascular Endothelial Growth Factor (VEGF) to its receptors. Normally, when VEGF is secreted by tumors it binds to target endothelial receptors and directs the profusion of new capillaries to supply the tumor with nourishment. By blocking the receptor sites, AE-941preempts the formation of the new blood supply the growing tumor needs to sustain itself.

AE-941 also inhibits the metastatic cellular machinery the tumor normally uses to disrupt the extracellular matrix of the surrounding host tissue. Additionally, the drug appears capable of inducing endothelial cell specific apoptosis and also of inducing an increase in endothelial cell production of compounds that may cause the disintegration of blood vessels already present within the tumor.

The anti-angiogenic and antitumor activity activity of AE-941 was first reported in 1997. It is now in Phase III trials in several countries for renal cell carcinoma and non-small-cell lung cancer. The literature also confirms the drug's efficacy in stabilizing tumor progression and relieving pain in metastatic prostate cancer patients. More recently, AE-941 has received attention as a possible treatment against metastatic breast cancer.

The drug's anti-angiogenic bioactivity further suggests it could be a valuable agent for use in patients suffering from multiple myeloma and other hematologic (blood) diseases. One of the characteristics of multiple myeloma is bone marrow angiogenesis, and treatment with an anti-angiogenic agent like neovastat shows potential.

From an ecological standpoint, commercialization and broadened chemotherapeutic use of AE-941 may be problematic. Although the drug extract is produced from only taxonomically identified shark species harvested under ostensibly sustainable conditions, long-term exploitation of already critically threatened natural shark populations should be avoided if at all possible.

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Falardeau P, Champaigne P, Poyet P, Hariton C, and E Dupont. 2001. Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Seminars in Oncology 28:620-5.

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.

The Cleveland Clinic. Multiple Myeloma Research Center (Industry website)
http://www.clevelandclinic.org/myeloma/neovastat.htm

BioPortfolio, LeadDiscovery report (Industry website)
http://www.bioportfolio.com/LeadDiscovery/PubMed-020210.htm