COX-2 inhibitors (used as painkillers) were pulled from the market due to increased risk of heart attack. Now they're learning the root cause of this increased risk:Study shows how painkillers raise heart risk.
It says: "FitzGerald has for years had a theory that COX-2 drugs depress a protective fat called prostacyclin, while leaving unaltered a harmful one called thromboxane."

Googling prostacyclin, I find (if I understand it properly) that this is a PROTEIN!
Human protein: P43119 - Prostacyclin receptor, and so is thromboxane (or at least thromboxane is a receptor that can be tinkered with via proteins).

And that if COX-2 inhibitors can be made safe, they can be used to treat colon cancer and breast cancer and Alzheimer's and that since COX-2 is an enzyme, I believe Rosetta work could be applied to replacing the original, problematic inhibitors in the first place.

This seems to imply that Rosetta work could be applied to: heart attacks, and mitigating the current increased risk posed by the COX-2 inhibitors, replacing the current COX-2 inhibitors with something better, and providing safe cancer treatments.

...am I putting pieces together here that don't fit? I mean I KNOW proteins are EVERYWHERE, and that truely understanding them is going to revolutionize modern pharmacology and medicine... but being readily able to apply the science to these areas really broadens your audience.

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Does anyone know if I've used the dots to draw a straight line; when a box is the only valid scientific connection?

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Hey Feet1st,

Thromboxane and prostacyclin are both derivatives of arachadonic acid (a 20 carbon fatty acid). The links you have are for the the RECEPTORS of these molecules (and the receptors ARE proteins)

There's a nice little picture in the Wikipedia here that shows the pathway from arachadonic acid. Basically, COX-2's inhibit the prostocyclin synthetase, so instead of making lets say 50 units of both, you make no prostocyclin and up to 100 thromboxanes.

But if you also knocked out the thromboxane receptor (so it can't have any effect on the cell) you'd have reduced chance of heart attack... but increased chance of hemophilia (thromboxane is needed for platelets to form blood clots).

Hope that helps a bit.

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...if you also knocked out the thromboxane receptor (so it can't have any effect on the cell) you'd have reduced chance of heart attack... but increased chance of hemophilia (thromboxane is needed for platelets to form blood clots).

Hope that helps a bit.

Sooo much to learn. I'm really out of my element here with the biochem that's at work here. ...So, you could stem the hemophilia risks with proper dosages, right? And all of the biological references to "receptors" are basically viable targets for Rosetta technology to be applied against, correct?

I understand that every action in the body has a reaction, which potentially is more harmful that what you were trying to resolve in the first place. So I'm not trying to say a proposed treatment would always be safe, effective and non-toxic. These are all things that would need to be resolved down-line from the synthesis of a new protein that will operate against the desired target. But, if one doesn't work in the desired mannar, you can devise others, and test those.

I am really just trying to see if I've got the scope of Rosetta correct here. If Rosetta drew a perfect line to the native protein structures... then you'd be able to resolve these problems with COX-2 inhibitors, right? Either by eliminating the adverse side-effects, or by killing pain in a different mannar altogether. Or by offsetting the increasing levels of the harmful compounds. Have I got it right?

Part of my point was that from these articles it seems pretty clear that if Rosetta were able to devise a new protein for such a problem, it sounds like all the rest of the science is in place to study, test and understand and prove it's effectiveness.

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I don't think you could resolve the Cox problems if we knew exactly what it looked like.

Think of it this way, you have water flowing down a river that splits into two channels. This upper part of the river is Arachadonic acid. It splits to the thromboxane and prostacyclin streams. But we live on the Prostocyclin, and our house is in danger of being washed away, so we block the Prostocyclin. But then ALL the water goes down the thromboxane, which floods our fields.

The arachadonic acid is going to turn into SOMETHING. and if it doesn't turn into something, it will build up, which could be toxic.

And you could treat the homophilia with drugs, but hemophilia generally is not considered an "acceptable" side effect to a drug.

BUT if we know the protein structures, we might be able to better anticipate side effects, and also make better second and third generation drugs (which generally have fewer side effects). The protein sturctures might also give us new places to try to block something.

So, if instead of making a cox 2 inhibitor, we could reduce the prostocyclin by degrading it faster (widening the stream in the example above), you would get a similar effect. knowing the protein that breaks down prostocyclin and making an activator for that protein would be easier if we know that protein's structure.

We can't make a magic bullet though, because the system will have to re-balance somehow.

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