Alagebrium

Alagebrium

Alagebrium

Chemical compound

Alagebrium (formerly known as ALT-711, dimethyl-3-N-phenacylthiazolium chloride) was a drug candidate developed by Alteon, Inc. It was the first drug candidate to be clinically tested for the purpose of breaking the crosslinks caused by advanced glycation endproducts (AGEs), thereby reversing one of the main mechanisms of aging.[1] Through this effect Alagebrium is designed to reverse the stiffening of blood vessel walls that contributes to hypertension and cardiovascular disease, as well as many other forms of degradation associated with protein crosslinking.[2] Alagebrium has proven effective in reducing systolic blood pressure[3] and providing therapeutic benefit for patients with diastolic heart failure.[4]

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Mechanism

Advanced glycation end-products (AGEs) are proteins that become glycated as a result of exposure to sugars.[5] They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney disease, and Alzheimer's disease. Pharmacologic intervention with alagebrium directly targets the biochemical pathway leading to AGEs. Although alagebrium may break some important AGE crosslinks, there is no evidence that it is effective against the most prevalent crosslink: glucosepane.[6]

History

Alteon said that it had selected ALT-711 as its lead AGE-breaker based on preclinical results in its annual report for the year 1997 and that it was preparing an IND filing.[7]

The INN name was proposed in 2004[8] and recommended in 2005.[9]

In 2006 Alteon merged with a company called HaptoGuard that had cash and a potential diagnostic test for haptoglobin; as part of the merger Genentech, which held preferred shares in Alteon, converted their shares to common ones and received the right to get milestone payments and royalties on sales of alagebrium, and option rights to license ALT-2074.[10] In 2007, the company changed its name to Synvista Therapeutics, Inc.[10] Synvista announced that it was terminating clinical trials of alagebrium in January 2009 in order to focus on the diagnostic test and another clinical candidate SYI-2074 (formerly ALT-2074).[11] The company seems to have discontinued operations and their website is no longer available.

See also

References

  1. [1]
    "R&D overview: A.G.E. crosslink breakers and Alagebrium". Alteon Corporation. Archived from the original on 1 July 2007. Retrieved 4 July 2007.
  2. [2]
    "Product Candidate: A.G.E. crosslink breakers". Alteon Corporation. Archived from the original on 1 July 2007. Retrieved 4 July 2007.
  3. [3]
    Bakris GL, Bank AJ, Kass DA, Neutel JM, Preston RA, Oparil S (December 2004). "Advanced glycation end-product cross-link breakers. A novel approach to cardiovascular pathologies related to the aging process". American Journal of Hypertension. 17 (12 Pt 2): 23S–30S. doi:10.1016/j.amjhyper.2004.08.022. PMID 15607432.
  4. [4]
    Little WC, Zile MR, Kitzman DW, Hundley WG, O'Brien TX, Degroof RC (April 2005). "The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure". Journal of Cardiac Failure. 11 (3): 191–195. doi:10.1016/j.cardfail.2004.09.010. PMID 15812746.
  5. [5]
    Goldin A, Beckman JA, Schmidt AM, Creager MA (August 2006). "Advanced glycation end products: sparking the development of diabetic vascular injury". Circulation. 114 (6): 597–605. doi:10.1161/CIRCULATIONAHA.106.621854. PMID 16894049.
  6. [6]
    Monnier VM, Sell DR (2006). "Prevention and repair of protein damage by the Maillard reaction in vivo". Rejuvenation Research. 9 (2): 264–273. doi:10.1089/rej.2006.9.264. PMID 16706654.
  7. [7]
    "Alteon 10-K For the fiscal year ended December 31, 1997". Alteon via SEC Edgar. 31 March 1998.
  8. [8]
    "Proposed INN: List 91" (PDF). WHO Drug Information. 18 (2). 2004.
  9. [9]
    "Recommended INN: List 53" (PDF). WHO Drug Information. 19 (1). 2005.
  10. [10]
    "10-K For the fiscal year ended December 31, 2007". Synvista Therapeutics. U.S. Securities and Exchange Commission. 15 March 2008 – via SEC Edgar.
  11. [11]
    Myers C (29 January 2009). "Synvista Therapeutics Announces Termination of Clinical Trials of Alagebrium and SYI-2074 and Provides Business Update". FierceBiotech.
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