Vascular targeting

Screening the molecular heterogeneity of receptor expression in endothelial cell surfaces is required for the development of vascular-targeted therapies. First, as opposed to targeting purified proteins as discussed above, membrane-bound receptors are more likely to preserve their functional conformation, which can be lost upon purification and immobilization outside the context of intact cells. Moreover, many cell surface receptors require the cell membrane microenvironment to function so that protein-protein interaction may occur. Finally, combinatorial approaches may allow the selection of cell membrane ligands in a functional assay and without any bias about the cellular surface receptor. Therefore, even as yet unidentified receptors may be targeted. 

Trepel M, Grifman M, Weitzman MD et al. Molecular adaptors for vascular-targeted adenoviral gene delivery. Hum Gene Ther 2000 11 1971-1981. 

Flavone-8-acetic acid (117) Flavone derivative ASA404 (DMXAA, ASA1404) (118) Oncology Vascular targeting and angiogenesis inhibition Phase III Antisoma (University of Auckland)/ Novartis 709-713... 

Landuyt W, Ahmed B, Nuyts S, et al. In vivo antitumor effect of vascular targeting combined with either ionizing radiation or anti-angiogenesis treatment. Int J Radiat Oncol Biol Phys 2001 49(2) 443-450. 

Nitric Oxide Synthesis as a Vascular Target for Dietary Isoflavones 252... 

NITRIC OXIDE SYNTHESIS AS A VASCULAR TARGET FOR DIETARY ISOFLAVONES... 

Combretastatin A4 phosphate (72) is a phosphate prodrug of combretastatin A4, a c/s-stilbene, isolated from Combretum caffrum (66). Combretastatin A4 is one of the many combretas-tatins that inhibits tubulin polymerization (67), shows efficacy against solid tumor, is a vascular targeting agent that blocks the blood supply to solid tumors, and is in Phase II/III clinical development for the treatment of various types of tumors as a vascular targeting agent (68-71). 

Eckhart AD, Ozaki T, Tevaearai H, Rockman HA, Koch WJ. Vascular-targeted overexpression of G protein-coupled receptor kinase-2 in transgenic mice attenuates P-adrenergic receptor signaling and increases resting blood pressure. Mol Pharmacol 2002 61 749-758. 

Milowsky MI, Nanus DM, Kostakoglu L, et al. Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors. / Clin Oncol. 2007 25 540. 

Schmidt-Erfurth U, Hasan T, Gragoudas E, Michaud N, Flotte TJ, Birngruber R. Vascular targeting in photodynamic occlusion of subretinal vessels. Ophthalmology 1994 101 1953-1961. 

Yoshioka, Y., Tsutsumi, Y., Nakagawa, S., Mayumi, T., Recent progress on tumor missile therapy and tumor vascular targeting therapy as a new approach. Curr. Vase. Pharmacol. 2004, 72, 259-270. 

ZD-6126 N-Acetyl-colchinol-phosphate (le) Phase II ongoing n.p. Astra Zeneca vascular targeting agent [22,23]... 

CA4P (Prodrug) (5c) Phase II 0.9-3 nM (drug) Oxigene INC vascular targeting agent [30,34,36 37]... 

Cooney MM, Ortiz J, Bukowski RM, et al. Novel vascular targeting/disrupting agents combretastatin A4 phosphate and related oompounds. Curr Onool Rep 2005 7 90-95. 

Tozer GM, Prise VE, Wilson J, Locke RJ, Vojnovic B, Stratford MRL. Combretastatin A-4 phosphate as a tumor vascular-targeting agent Early effects in tumors and normal tissues. Cancer Res 1999 59 1626-1634. 

Trachtenberg J, Bogaards A, Weersink RA, Haider MA, Evans A, McCluskey SA, Scherz A, Gertner MR, Yue C, Appu S, Aprikian A, Savard J, Wilson BC, Elhilali M. Vascular targeted photodynamic therapy with palladium-bacteriopheophorbide photosensitizer for recurrent prostate cancer following definitive radiation therapy Assessment of safety and treatment response. J Urol 2007 178 1974—1979. 

Reddy GR, Bhojani MS, McConville P, et al. Vascular targeted nanoparticles for imaging and treatment of brain tumors. Clin Cancer Res 2006 12 6677-6686. 

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