Denosumab is an antibody that blocks the RANK ligand, a protein that tells the body to remove bone.
Macrocycles offer a number of advantages over bigger biologics, including better ligand efficiency, tissue penetration, delivery, and cost.
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It turns out that in excess quantities, acetaminophen's breakdown products latch on to the FAS ligand of liver cells.
Cells have receptors on their surface that, when the right key (or ligand) is inserted, cause them to change.
"I don't think we're going to find the magic bullet--but we're going to get closer, " says Andres Negro-Vilar, chief scientific officer at Ligand Pharmaceuticals.
In osteoporosis the RANK ligand protein is all too effective in producing the breakdown effect, resulting in debilitating hip fractures in postmenopausal women and others.
The drug is a bioengineered antibody to a crucial natural protein called Rank-ligand that appears to play a central role in initiating the bone breakdown process.
Behan, a native of Liverpool, England with a doctorate in biochemistry, believed he could come up with drug candidates without knowing the ligand part of the equation.
Upon ligand engagement, these receptors in turn engage MyD88 which signals through IRAK4 to turn on a variety of pathways, including NF-kB and the secretion of pro-inflammatory cytokines.
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In the last two years the instruments have been employed in deals proposed by Sanofi-Aventis ( NYSE:SNY), AstraZeneca ( NYSE:AZN) and Ligand Pharmaceuticals ( Nasdaq:LGND), among many others.
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Drugmakers looked for proteins called ligands, which dock to specific GPCRs, and then created a drug that either blocked or enhanced the ability of the ligand to connect with its receptor.
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