Kinase

[Ricorocks]

Can't find the 'papers' regarding kinase based research.

If kinases are enzymes (proteins) associated with phosphate, are kinases inter-cellular, at the 'mitochondria' and necessary for ATP, like in the krebs/citric acid cycle? Are kinase based meds. considered a 'class' of drug (aka *.statins)? Do kinase based drugs assist or slow down ATP. Was it a hurdle, or FAH related, to get the drug past the cell membrane?

Note I kind of remember the third phosphate bond (ATP) being not stable or 'cleaved' to produce energy, is that the kinase function?

What's an example of a kinase based drug 'name', assume many exist from diff mfg.??

[Joe_H]

Dr Pande posted in the Where Can I Learn More? topic a link to search PubMed and create a list of Pande Group papers. A quick glance at that search has the 6th paper listed being on a kinase. The list runs to over 200 papers, I don't know if that list includes papers from the other members of the Folding@home Consortium. If not, a similar search can be made based on members of those research groups.

[7im]

Google kinase based drug, or kinase inhibitor. The U of G will likely be more instructional. Unfortunately, this section of the forum is kind of a legacy feature. The researchers in the project used to spend more time here and answer a few questions like this from time to time. But they usually end up getting very deep very quickly, beyond the casual folder's grasp of that level of science.

Otherwise this would need to be posed directly to the project staff on Reddit.

[Ricorocks]

Thanks Guys! Gleevec is a drug based on 'kinase' so perhaps this drug came about, with the help of FAH. I understand difficult to impossible for a direct link

[7im]

Thanks Guys! Gleevec is a drug based on 'kinase' so perhaps this drug came about, with the help of FAH. I understand difficult to impossible for a direct link

TBH, I don't know of any drugs related to FAH results, yet. I think if there were, it would be well advertised already.

[bruce]

The companies which develop drugs are doing so in order to patent and then sell that drug. Trade secrets and anticipated profits are a strong motivators. Universities use FAH to perform BASIC research and results are placed in the public domain (available to anyone). The drug developer is welcome to use FAH's research but the named drug belongs to the drug company, not to Stanford or other FAH research facilities. Somewhere in the fine print credit might be given to FAH and other sources, but you'll probably never see it.

FAH's final results are the published research papers, not the drugs.

[Ricorocks]

Bruce thank you, but your comments were well understood & then some, prior to your post! What is being asked is rather difficult without, clearcut lineage. From the public domain knowledge from FAH, who may have used some of that knowledge in developing med's.

Example. Gleevec is a kinase, based med. Did FAH help in development? This becomes Fuzzy here, as knowing, how or what uses public domain knowledge, i put to is truly known by the mfg. Seeing this a little more fully, would/could be helpful in seeing the 'big picture.

Fah project > WU > write up > public domain > mfg found useful in making X

I previously asked does FAH get a thank you note from industry. Does industry support or recognize & in what way FAH.

Back to Gleevec, given the contribution in kinase, by FAH it seems likely, that mfg. might have, in some way, benefited from the WU's. Yes best answered by mfg., however, It's a little impractical to converse with them.

Again after public domain, it becomes blurry/fuzzy how the knowledge, contributed.

[Joe_H]

Using your example of Gleevec, it was approved for use in the US for medical purposes in the 2001-2 timeframe. So it is a drug that definitely predates Folding@home. Other drugs connected to kinases can also be looked up for when they were approved for use, given the research and development that would need to have been done adding on another 10-15 years can give a pretty good idea of when the potentially useful drug was first identified. I suspect most of the drugs currently in use would date back to the late 80's or into the 90's at least.

However that is not to say that FAH has no contribution to make in connection to these drugs already available. Almost all of these drugs have side effects, or counter-indications based on specific metabolic issues patients have. Folding research may help identify why the drug has these issues and possibly suggest alterations in the chemical composition that would result in either fewer side effects and/or better therapeutic action. Another thing that might be identified are adjuncts that can be used in conjunction with an existing drug to limit its effects on noncancerous cells.

That last item is of personal interest. Seven years ago I went through treatment for Stage 3 colorectal cancer, and as part of that treatment received the chemotherapy drug oxaliplatin. I, like a significant percentage of recipients, developed chemotherapy induced peripheral neuropathy (CIPN) which still affects the nerves in my feet. Just a couple of years ago I came across a journal article that had just been published, it presented the results of a study where administering an adjunct drug they had identified with oxaliplatin reduced the incidence of CIPN by about 50%. Too late to help me, but I would definitely applaud anything that helped someone avoid this in the future.

[Ricorocks]

Ah ha! The contributions by donors, will most likely be seen in new or future drugs. Lead time, before approval & FAH's relatively short history, shows why, what I'm asking is problematic.
FAH's contribution/knowledge may lead, to 'adjunct' drugs being given to reduce side effects. Interesting & no possible way of knowing, when or how, as it's mfg stumbling upon improvements.

I'm happy your still around to answer rookie questions, must have been scary times for you & your family. Did the adjunct drug/oxalipatin study lead to new treatment protocol?

Take Care & Thanks
Rick

[Joe_H]

I don't know if that study led to a new treatment protocol, but that was proposed in the abstract. From what I was seeing checking on treatment protocols while being treated myself, it often takes several studies to confirm results and for a new variation in a treatment protocol to be accepted. Then after that is the issue of getting insurance providers to accept the changed protocol as standard treatment.

At some time I will try and find that article again and see if it was followed up on. Just came across the article while at work where part of my job is fulfilling interlibrary requests for journal articles to other institutions for articles in databases we have subscriptions to.

You mentioned "stumbling upon improvements". As I understand it, one goal researchers have in trying to understand the protein folding process and its relation to diseases is to be able to know the conformation of active sites. Then that would lead to the ability to look for drugs that have the exact shape to fit where they want it to and not elsewhere. There are a number of different approaches to achieving that goal, folding is one of them.

[bruce]

THere's a lot that happens AFTER FAH publishes a paper. Assuming some employee of a drug company is keeping up with current research, something they read will spark their thinking and they'll propose a new project which may lead to animal testing and human testing an eventually something may be approved by the FDA and become named drug. By the time all that happens, the employee will probably have forgotten what sparked his imagination so no ThankYou will ever be written. Even if his proposal for a new project happens to mention a FAH research paper, by the time the drug emerges that's an incidental piece of information

That's just the nature of research that's published in the public domain..