Drugs 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. 

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. 

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

Sunitinib maleate (1, Sutent, SU11248) was discovered by Sugen, which later became part of Pfizer. It is an orally active drug that exhibits potent anti-angiogenic activity through the inhibition of multiple RTKs. Specifically, 1 inhibits vascular... 

Microelectromechanical systems (MEMS) devices can potentially administer complex dosing patterns using very small amounts of drugs. This system could be used to deliver protein molecules intraocularly such as neuroprotectors or anti-angiogenic molecules. Delivery of chemotherapeutic agents using the MEMS may also be a future possibility. 

Based on the results described above, Eyetech received Food and Drug Administration approval to market pegaptanib sodium for treatment of patients with neovascu-lar AMD. This drug is the first anti-angiogenic agent to receive approval to treat AMD. 

Anti-angiogenic activity of selected receptor tyrosine kinase inhibitors, PD 166285 and PD 173074, implications for combination treatment with photodynamic therapy. Invest New Drugs, 17, 121-135. 

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