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Chemical Compound Review:

Antrin (rat) (3S)-4-[(2S)-2-[[(1S)-1- [[(1S)-1-[[(1S)-1...

Synonyms: AC1MIZ73, 112173-60-1, Preprosomatostatin (25-34), Ala-pro-ser-asp-pro-arg-leu-arg-gln-phe

Chou, T.M. et al., Yeung, P.F., Galanopoulou, A.S. et al., Benoit, R. et al., Benoit, R. et al., et al.

Chou, Woodburn, Cheong, Lacy, Sudhir, Adelman, Wahr, Rockson, Kramer, Razavi, Szuba, Filardo, Fitzgerald, Cooke, Yousuf, DeVault, Renschler, Adelman,

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Disease relevance of Ala-pro-ser-asp-pro-arg-leu-arg-gln-phe

Pharmacyclics is developing the photosensitizer, motexafin lutetium as Antrin for the potential treatment of restenosis and atherosclerotic plaques, Lutrin for the possible treatment of cancer, and Optrin for the possible treatment of age-related macular degeneration (AMD) [1].

High impact information on Ala-pro-ser-asp-pro-arg-leu-arg-gln-phe

By using an antibody against the amino terminus of prosomatostatin, a decapeptide with the structure Ala-Pro-Ser-Asp-Pro-Arg-Leu-Arg-Gln-Phe, corresponding to preprosomatostatin (25-34), was isolated from the endocrine portion of the rat stomach, the gastric antrum [2].
Prosomatostatin-derived antrin is present in gastric D cells and in portal blood [3].
COS-7 and PC12 cells expressed only furin, secreted constitutively, and processed PSS preferentially at monobasic sites to SS-28 (40-43%) and antrin (27-29%) [4].
Mammalian prosomatostatin (PSS) is cleaved at a dibasic Arg-Lys site to produce somatostatin-14 (SS-14) and at monobasic Arg and Lys sites to yield SS-28 and PSS(1-10) (antrin), respectively [4].
Antrin phototherapy generates cytotoxic singlet oxygen that has been shown to induce apoptosis in macrophages and smooth muscle cells [5].

Anatomical context of Ala-pro-ser-asp-pro-arg-leu-arg-gln-phe

Antrin, which corresponds to proSS(1-10), reaches its highest concentration in the antral portion of the stomach (117 +/- 13 pmol/g wet weight), where it is found in secretory granules of delta cells [6].
The safety, tolerability, and preliminary efficacy of Antrin phototherapy has been assessed in a phase 1 dose-ranging clinical trial in subjects with peripheral artery disease and is currently being examined in a phase 1 study in subjects with lesions of the native coronary arteries undergoing stent implantation [5].
BACKGROUND: Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells [7].

Associations of Ala-pro-ser-asp-pro-arg-leu-arg-gln-phe with other chemical compounds

Photoangioplasty for human peripheral atherosclerosis: results of a phase I trial of photodynamic therapy with motexafin lutetium (Antrin) [8].

Analytical, diagnostic and therapeutic context of Ala-pro-ser-asp-pro-arg-leu-arg-gln-phe

The preliminary results suggest that Antrin phototherapy is safe, well tolerated, and nontraumatic [5].
It is designed to evaluate Antrin photoangioplasty as a primary treatment for PAD and for the prevention of restenosis following balloon angioplasty [341341,347151] [1].

References

Motexafin lutetium (Pharmacyclics). Yeung, P.F. IDrugs : the investigational drugs journal. (2001) [Pubmed]
A new prosomatostatin-derived peptide reveals a pattern for prohormone cleavage at monobasic sites. Benoit, R., Ling, N., Esch, F. Science (1987) [Pubmed]
Prosomatostatin-derived antrin is present in gastric D cells and in portal blood. Ravazzola, M., Benoit, R., Ling, N., Orci, L. J. Clin. Invest. (1989) [Pubmed]
Heterologous processing of prosomatostatin in constitutive and regulated secretory pathways. Putative role of the endoproteases furin, PC1, and PC2. Galanopoulou, A.S., Kent, G., Rabbani, S.N., Seidah, N.G., Patel, Y.C. J. Biol. Chem. (1993) [Pubmed]
Photodynamic therapy: applications in atherosclerotic vascular disease with motexafin lutetium. Chou, T.M., Woodburn, K.W., Cheong, W.F., Lacy, S.A., Sudhir, K., Adelman, D.C., Wahr, D. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions. (2002) [Pubmed]
Processing of prosomatostatin. Benoit, R., Esch, F., Bennett, H.P., Ling, N., Ravazzola, M., Orci, L., Mufson, E.J. Metab. Clin. Exp. (1990) [Pubmed]
Phase I drug and light dose-escalation trial of motexafin lutetium and far red light activation (phototherapy) in subjects with coronary artery disease undergoing percutaneous coronary intervention and stent deployment: procedural and long-term results. Kereiakes, D.J., Szyniszewski, A.M., Wahr, D., Herrmann, H.C., Simon, D.I., Rogers, C., Kramer, P., Shear, W., Yeung, A.C., Shunk, K.A., Chou, T.M., Popma, J., Fitzgerald, P., Carroll, T.E., Forer, D., Adelman, D.C. Circulation (2003) [Pubmed]
Photoangioplasty for human peripheral atherosclerosis: results of a phase I trial of photodynamic therapy with motexafin lutetium (Antrin). Rockson, S.G., Kramer, P., Razavi, M., Szuba, A., Filardo, S., Fitzgerald, P., Cooke, J.P., Yousuf, S., DeVault, A.R., Renschler, M.F., Adelman, D.C. Circulation (2000) [Pubmed]

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