Non-steroid nuclear receptors

With all this data available, you'd think the makers of aspirin and ibuprofen would be touting anti-cancer benefits of their products (which they can legally do, given the extensive nature of the scientific evidence), and you'd think the Food and Drug Administration, the Centers for Disease Control, and other agencies charged with promoting public health would be quick to spread the word. Not so, however. There's too much money to be made treating cancer, after it takes root. For example, Pfizer subsidiary Wyeth Pharmaceuticals (makers of Advil) also sells the anti-cancer drug Torisel, which, at $76,000 per gram is several times more expensive than plutonium . Likewise, Bayer makes anti-cancer drug Nexavar, which costs $69,000 for a year of treatment . With these and other exorbitantly priced drugs at risk, there is no incentive for the Bayers or Pfizers of the world to undercut future profits by telling people about the anti-cancer benefits of cheap over-the-counter NSAIDs.

Thus a local conformational change initiated by the agonist, but not antagonist binding results in a destabilization of the protein structure. This destabilization is not strong enough to denature the protein, but results in a long range effect across the protein affecting its active site several angstrom away from the ligand binding site. This is known as an allosteric mechanism. As a rule, agonists induce structure destabilization, while antagonists merely bind , but do not affect the protein structure (or trigger a conformational change that locks a protein in its inactive position). One way to visualize the action of ligands on receptors is to realize that proteins constantly undergo conformational changes which is best described as an equilibrium between an active and inactive, or even among multiple states, including desensitized states (different types of inactive states). Agonists and antagonists shift this equilibrium towards an active or inactive conformation, respectively.

Non-steroid nuclear receptors

non-steroid nuclear receptors

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