Drug.....for?

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boboviz

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Message 4601 - Posted: 19 Jan 2017, 11:29:18 UTC
Last modified: 19 Jan 2017, 11:29:49 UTC

Ok, we are crunching for finding new drugs.
But for diseases....cancer? SLA?? Parkinson?
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Andrew VoronkovProject donor
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Message 4603 - Posted: 19 Jan 2017, 16:00:32 UTC - in response to Message 4601.  

Ok, we are crunching for finding new drugs.
But for diseases....cancer? SLA?? Parkinson?


Right now we are developing methods for polyharmacological drugs development. Dual-targeting drugs.
As case study is taken goal to develop Tankyrase and PI3K inhibitors for treatment of colorectal cancer. This is relevant to other cancers as well. Especially are targeted those cancers, which have cancer stem cells actively involved and cancers on metastasis stage.

The currently dominating concept is "one target-one drug". Target means for example protein (in most cases), but can be DNA, RNA etc.
But most of the drugs are promiscuous, so even so called "one-target" drugs usually target something else also and usually this leads to side effects. Most of the approved drugs have side effects, but just less damaging than disease.
Polypharmacology concept suggests that making drugs, targeting more than one target (dual-targetin for example) will reduce side effects and may increase efficiency per quantity of the drug used.

So, polypharmacology:
1. Less side effects
2. More efficient
3. Cheaper
Currently we have selected two biotargets - Tankyrase (my postdoc expertise in one of the leading labs, in Norwegian Cancer cluster) and PI3K (its inhibition is synergistic to tankyrase).
So we are doing two things - developing new molecules and developing methods for polypharmacology.


We are doing this using three software programs for DrugDiscovery@home:
GROMACS - molecular dynamics
Autodock Vina - molecular docking
Autodock Smina - fork of Vina. It allows more customization and usage of our own (or just external) scoring functions. That is a very important change.

We are also using pharmacophore-based screening, QSAR and ADME/Tox filtering, but those are not computing power demanding for the amount of compounds, which we process now (starting database is around 3-4 mln compounds). After filtering we got database of 750 K compounds.

We have some preliminary agreements with MIPT (Moscow Institute of Physics and Technology) and Stanford University for testing the compounds, which we´ll find perspective.

The main scientific part now - is working on more or less universal consensus scoring function for Smina.

We also want to participate in D3R challenge (https://drugdesigndata.org/about/grand-challenge).
Unfortunately I´ve got information about this challenge only last week and not so much time left to participate.
However, we plan to participate in different kinds of international challenges.

So, on top of competition to crunch, there will be also competition in methods application toward tasks, participation in international competitions.
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boboviz

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Message 4610 - Posted: 20 Jan 2017, 16:17:25 UTC

Very interesting!!!!
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Gunde

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Message 4613 - Posted: 20 Jan 2017, 17:56:27 UTC

Thanks for info
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Message 4637 - Posted: 21 Jan 2017, 16:11:06 UTC - in response to Message 4613.  

Just for example. We now have collaborators from two leading universities in UK and USA.
But I am even afraid to say which ones from confidentiality point of view (because competing groups and companies can easily identify whom from knowledge of biotarget and University) etc.
So that is how pharmaceutical industry works.
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Mercosity

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Message 4807 - Posted: 13 Mar 2017, 10:21:29 UTC

Please information update..
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boboviz

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Message 4827 - Posted: 31 Mar 2017, 7:09:48 UTC - in response to Message 4637.  

So that is how pharmaceutical industry works.


For me the important part is that results will be public.
After that, if a drugmaker wants to use this results, no problem
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Jim1348

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Message 4894 - Posted: 6 Aug 2017, 21:37:12 UTC - in response to Message 4827.  

For me the important part is that results will be public.
After that, if a drugmaker wants to use this results, no problem

I wonder if they are doing the same type of work now, after the split? What are the targets?

But the important thing for me is that the results get used. Whether they are published is irrelevant. In fact, that could destroy the incentive of a drug company to market them, if they know they will have a lot of competitors. Then, no one makes the drug, because the costs of testing and marketing it can not be recovered by the sales price. So in effect the drug becomes generic immediately, with no chance for the company that put forth the effort to market it to recover their investment and make a profit.

I avoid projects (at least one thus far) where they make it clear that no one can make any money from the research. It is useless to put forth computer effort on something that can't possibly be brought to market.
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boboviz

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Message 5140 - Posted: 27 Oct 2017, 7:09:03 UTC - in response to Message 4894.  
Last modified: 27 Oct 2017, 7:10:09 UTC

But the important thing for me is that the results get used. Whether they are published is irrelevant. In fact, that could destroy the incentive of a drug company to market them, if they know they will have a lot of competitors. Then, no one makes the drug, because the costs of testing and marketing it can not be recovered by the sales price.


Public must be the "teoretical concept" of research. See the European program Horizon 2020.
Practical results may be private (drug company).

Despite this discussion, i'm curious: there are some preliminary results of DD@H? Are the data ok for researchers?
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