targeted secretion inhibitors—innovative protein therapeutics有针对性的分泌inhibitors-innovative蛋白质疗法.pdf

Toxins 2010, 2, 2795-2815; doi:10.3390/toxins2122795 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Targeted Secretion Inhibitors—Innovative Protein Therapeutics Foster Keith * and Chaddock John Syntaxin Ltd, Units 4-10 The Quadrant, Barton Lane, Abingdon, OXON, OX14 3YS, UK; E-Mail: john.chaddock@ * Author to whom correspondence should be addressed; E-Mail: keith.foster@; Tel.: +44-1235-552114; Fax: +44-1235-552200. Received: 15 October 2010; in revised form: 16 November 2010 / Accepted: 2 December 2010 / Published: 3 December 2010 Abstract: Botulinum neurotoxins are highly effective therapeutic products. Their therapeutic success results from highly specific and potent inhibition of neurotransmitter release with a duration of action measured in months. These same properties, however, make the botulinum neurotoxins the most potent acute lethal toxins known. Their toxicity and restricted target cell activity severely limits their clinical utility. Understanding the structure-function relationship of the neurotoxins has enabled the development of recombinant proteins selectively incorporating specific aspects of their pharmacology. The resulting proteins are not neurotoxins, but a new class of biopharmaceuticals, Targeted Secretion Inhibitors (TSI), suitable for the treatment of a wide range of diseases where secretion plays a major role. TSI proteins in