AE-941 is a naturally occurring anti-angiogenic compound, extracted from cartilage, with multiple anti-angiogenic mechanisms of action that provide broad therapeutic potential for a number of diseases. It is currently in international Phase III trials for renal cell carcinoma and non-small-cell lung cancer.
Investigated for use/treatment in kidney cancer, lung cancer, macular degeneration, multiple myeloma, prostate cancer, and psoriasis and psoriatic disorders.
Mechanism of action
AE-941(Neovastat) contains a component that specifically prevents the binding of VEGF (Vascular Endothelial Growth Factor) to its receptors. It inhibits gelatinolytic and elastinolytic activities for MMP-2, MMP-9, and MMP-12. The MMP's are often over expressed in tumors and play an important role in the degradation of the matrix that surrounds the cell (extracellular matrix), which allows tumor growth and invasion (metastasis). It also induces apoptosis (programmed cell death) which is an additional Anti angiogenic activity found in Neovastat.
Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly...
May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.