Alendronate

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Alendronate (Fosamax®)

Alendronate is commonly known for its use in treatment and prevention of osteoporosis in postmenopausal women and men, but is also used to treat Paget's disease (disease that results in deformed and enlarged bones).[1] Alendronate belongs to the class of nitrogen-containing bisphosphonates, which are inorganic pyrophosphate analogues.

History of Bisphosphonates

Bisphosphonates were first synthesized in Germany in 1865, but were not studied biologically until 1968. In the interim time, they were used in the textile and fertilizer industries due to their apparent inhibitory effect on calcium carbonate. However, in 1968, a group in Switzerland found inorganic pyrophosphates in urine and plasma. In vitro testing of these molecules revealed that they inhibited calcium phosphate precipitation and dissolution, but were destroyed in vivo by phosphatases. These results led to the discovery of bisphosphonates, as they reacted in the prescribed manner.[2]

Sodium alendronate was first marketed in 1994 as Fosamax® by Merck pharmaceutical. In 2008, Merck lost their U.S. patent on alendronate, allowing Barr Pharmaceuticals and Teva Pharmaceuticals USA to begin marketing generic forms of sodium alendronate. Other brand names for the drug include Fosamax+D®, Adronat, Alendros, Arendal, and Onclast.[3]

Structure

Image:Alendronate.gif[4] Alendronate is a nitrogen-conatining bisphosphonate with


Target Protein

Shown: The asymmetric subunit of FPPS, not the assumed biological molecule.

Drag the structure with the mouse to rotate


Natural Substrates

Image:IPP.png[5]

Isopentenyl pyrophosphate (IPP) actually binds to and stabilizes the alendronate-FPPS complex, rather than competing with the inhibitor.

Side affects of Drug

References

  1. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/
  2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138713/?tool=pmcentrez
  3. http://www.drugbank.ca/drugs/DB00630
  4. Image from: http://pharmacy-and-drugs.com
  5. Image from: http://reference.findtarget.com

Proteopedia Page Contributors and Editors (what is this?)

Anne Goodling, David Canner, Justin Myles Kidd, OCA

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