Anti-angiogenic

Though a large number of small molecule inhibitors against a variety of tyrosine kinases are being developed, the most advanced drugs can be roughly classified as (i) Bcr-Abl/Src family kinase inhibitors, (ii) ErbB inhibitors and (iii) broad spectrum TfCIs with an anti-angiogenic component. 

Paris D, Ait-Ghezala G, Mathura VS, Patel N, Quadros A, Laporte V, et al. Anti-angiogenic activity of the mntant Dntch A(beta) peptide on human brain microvascular endothelial cells. Brain Res Mol Brain Res 2005 136 212-30. 

Synthesis and characterization of a new class of anti-angiogenic agents based on ruthenium clusters... 

Figure 4 Anti-angiogenic activity of 1 and 3. (A) Angiographic images of the developmental CAM (EDD 9) treated with 0.9% NaCl (control) and 1 and 3 (150 pM/day). The vasculature is visualized by FITC-dextran fluorescence angiography (25 mg/kg, 20 kDa, XCK = 470 nm, Xem = 520 nm).

Nowak-Sliwinska, P., Ballini, J. P., Wagnieres, G. 8c van den Bergh, H. Processing of fluorescence angiograms for the quantification of vascular effects induced by anti-angiogenic agents in the CAM model. Microvasc. Res. 79, 21-28 (2010). 

How to cite this article Nazarov, A. A. et al. Synthesis and characterization of a new class of anti-angiogenic agents based on ruthenium clusters. Sci. Rep. 3, 1485 DOL10.1038/ srep01485 (2013). 

Kim SH, Jeong JH, Lee SH, Kim SW, Park TG (2006) PEG conjugated VEGF siRNA for anti-angiogenic gene therapy. J Control Release 116 123-129... 

The thalidomide analogs CPS49 (30) and CPS11 (31) have been reported to inhibit PI3/AKT signaling in multiple myeloma cells via an anti-angiogenic effect. These compounds are devoid of the teratogenic properties seen with thalidomide and are currently in preclinical development [66]. Compound 30, and to a lesser extent 31, induced a dose-dependent inhibition of proliferation in several multiple myeloma cell lines and reduced phospho-AKT levels [66]. These compounds also inhibited DNA synthesis in cell lines resistant to conventionally used anti-multiple myeloma drugs (e.g. dexamethasone, anthracyclines and melphalan) in a dose-dependent manner. 

Janssen A, et al. Peptide-targeted PEG-liposomes in anti-angiogenic therapy. Int J Pharm 2003 254 55. 

Sin N, Meng L, Wang MQW, Wen JJ, Bommann WG Crews CM. (1997) The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proc Natl Acad Sci USA 94 6099-6103. 

Gervaz P, Fontolliet C. (1998) Therapeutic potential of the anti-angiogene-sis drug TNP-470. Int J Exp Pathol 79 359-362. 

In 2006, Jung et al. described the anti-angiogenic activity of the artemisinin monomers 52-60 using vascularized chorioallantoic membranes of chicken embryo as an in vivo model. These compounds, at concentrations as low as 5 nmol/egg, inhibited angiogenesis process by 29-75%. Monomer 60 was found to be the most effective among the tested compounds. ... 

It should be noted, however, that mechanisms of action of most anti-angiogenic compounds are not well understood at present. For example, trombospondrn-1 (TSP-1) is able to inhibit tumour-associated angiogenesis, but when TSP-1 pellets were implanted into the ankles of AIA rats, it enhanced joint swelling and body weight loss in a dose- and time-dependent manner. These, possibly indirect, effects may be due to the involvement of TSP-1 in cell adhesion, as well as to its interactions with other adhesion molecules and inflammatory mediators [125]. 

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