Article

AE-941 (Neovastat): a novel multifunctional antiangiogenic compound.

Laboratiore de médicine moléculaire Hôpital Ste-Justine-UQAM, Centre de cancérologie Charles-Bruneau, Centre de Recherche de l'Hôpital Ste-Justine, 3175, Chemin Côte-Ste-Catherine, Montréal, Québec H3T 1C5, Canada.
Expert Review of Anti-infective Therapy (Impact Factor: 3.06). 11/2001; 1(3):341-7. DOI: 10.1586/14737140.1.3.341
Source: PubMed

ABSTRACT AE-941 (Neovastat) is a naturally occurring product extracted from cartilage and has antiangiogenic properties. It has reached Phase III clinical trial evaluation for the treatment of solid tumors (non-small cell lung cancer and renal cell carcinoma) and a pivotal Phase II clinical trial in multiple myeloma is ongoing. AE-941 inhibits several steps of the angiogenesis process, including matrix metalloproteinase activities and VEGF signaling pathways. Moreover, AE-941 induces endothelial cell apoptosis and tissue-type plasminogen activator activity, thus suggesting that it is a multifunctional antiangiogenic drug. Results from Phase I/II clinical trials indicate that AE-941, given orally, is well tolerated. Moreover, the median survival time in patients with renal cell carcinoma and non-small cell lung cancer was significantly longer in patients receiving high doses of AE-941 compared to low doses.

2 Bookmarks
 · 
138 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIM:To study the relationship between gastric carcinogenesis and angiogenesis. METHODS:Experimental model of gastric precancerous lesions and carcinomas was established in rats by chemical carcinogen, N-methyl-N'-nitro-soguanidine (MNNG). The specimens were collected in groups at different time points from pre-malignant precursor to gastric carcinoma, the sections were stained by HE and angiogenesis was observed. Tissue sections were also immunohistochemically stained for CD34 antigen, a marker for endothelial cells, and the microvessels were counted.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vascular endothelial growth factor (VEGF) is a crucial growth factor that mediates tumor angiogenesis, and thus many therapeutic agents are being developed to target VEGF or its receptors in the treatment of cancer. Early-phase clinical data indicate that such agents are effective and might lack the nonspecific toxicities of conventional chemotherapies. The anti-VEGF antibody bevacizumab has also shown promising efficacy in Phase III studies. Further research is required, especially into patient selection, the autocrine and paracrine VEGF effector functions in different malignancies, and the long-term safety of these compounds, but it is probable that VEGF and its receptors will soon be important targets in the treatment of cancer.
    Targets. 01/2003; 2(2):48-57.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that form a family of 24 members in mammals. Evidence of the pathological roles of MMPs in various diseases, combined with their druggability, has made them attractive therapeutic targets. Initial drug discovery efforts focused on the roles of MMPs in cancer progression, and more than 50 MMP inhibitors have been investigated in clinical trials in various cancers. However, all of these trials failed. Reasons for failure include the lack of inhibitor specificity and insufficient knowledge about the complexity of the disease biology. MMPs are also known to be involved in several inflammatory processes, and there are new therapeutic opportunities for MMP inhibitors to treat such diseases. In this Review, we discuss the recent advances made in understanding the role of MMPs in inflammatory diseases and the therapeutic potential of MMP inhibition in those conditions.
    Nature reviews. Drug discovery. 11/2014;