Week 2 Post 1

Week 2 video 1
-Drugs are expensive to produce. In fall 2014 it was estimated it costs $2.5 Billion dollars. This is why drugs are mainly only produced for common diseases or life threatening illnesses, as to make profit.
-In Target based drug discovery (TBDD), Molecular biologists inspect a cell to try to determine how the disease works and what is going on in the body pertaining to this disease.
-Proteins in the cell are the potential points of intervention, and that is what the drug effects.
-One protein is targeted by the molecular biologists, and then they develop a test called a binding assay, which is a test that can be done in test tubes to see if a certain molecule will bind to proteins.
-Chemists then send tens of thousands to over a million of possible molecules to test to see how well the moleecules will bind to the protein. These reactions are equilibrium reactions meaning they look at the value of the equilibrium constant K, and are looking for the smallest value as to favor the side that binds to the proteins
-the scientists are looking for Hits, meaning a K value of 10^-6 molar. after screening all the molecules, one might have 1000s of hits. then, the most promising hits based on cell permeability, how its metabolized, and if its patent-able
-The most promising become leads, of which one might have 1-5 leads
-the leads will be synthesized and altered slightly to try to improve the K value, to get it down to 10^-8 perhaps
-the leads are then tested on animals to check for toxicity
-if promising, it will be sent into the the FDA and will complete a Investigational Drug Application. if FDA say its all good, you can begin clinical trials on humans
-Phase 1 is a very small group of healthy volunteers (maybe 10-20) to check for toxic effects in humans
-Phase 2 is a bigger group (100-200) of patience that actually have the disease and check for more safety as well as efficacy and dosage information
-Phase 3 is an even bigger group of patients (1000-2000) to see if drug works over a more broad population like ethnic groups, age groups, and those with other health conditions
- if everything looks good, it is sent to the FDA and it will be approved under the New drug application, and then turns from a lead to a drug.
-even when its available to the public, it is still monitored for safety.
-The process from animal testing to market release is 10 years, the hit dicovery can vary greatly

Video 2
two types of drug discovery target and phenotype
-target based is what was in the previous video, and more common
-disadvantage of target based, is the assumption that your target protein will have a significant biological effect, if protein isn't effective then the molecule won't be effective
-phase 2 is where it is discovered the a drug will have low efficacy and that is a lot of work for a failed drug
-phenotypes are any observable characteristic in an organism
-drugs can change phenotype
-doesn't have to be an animal, it can be a tissue sample
-phenotype based starts with knowledge about a molecule that has an effect on phenotype
-for example if in a part of the world people eat a certain leaf and get drowsy, that molecule can help be a cure for insomnia
-this is the lead in phenotype based drug discovery
-your lead already has efficacy very important 
-then test lead in organism not people. This takes a lot longer, as you are resting in cells and so lead optimization is slowed
-almost certain the compound will have efficacy 
-target based has become prominent method as molecular bio has advanced
-some say the efficacy is poor with target and we need to go back to what drug discovery has done historically and do phenotype based
-target based is what I will be learning mostly

Video 3
-drugs are intellectual property and can be patented and trademarks and trade secrets and registered designs
-trademarks are the name brand of a drug. Most be registered in the country they are sold. No time limit as long as the company is willing to pay for the rights 
-Tylenol is a drug trademark, and only the company that has the rights to the name Tylenol can sell that drug under the name Tylenol 
-the same structure is sold under many other names however, isn't eh United States it is called acetaminophen, and in other countries called paracetamol these are generic names
-people pay more for the trademark name as it has an associated quality attached to the name
-patents allow a 20 year window in which a company can sell a product exclusively in exchange for publicly showing what it is and how it works 
-in drug industry, that window can sometimes be extended
-when drugs are patented, you are patenting the composition of matter
-also can cover dosing ideas or how it's formulated
-usually patented when being tested on animals, so at time the patent is filed it's a lead, not yet a drug
-once filed, they have a 20 year clock to try to make back their investment on this drug
-from animal trials to market takes about 10 years that is lost on patent and isn't making any money (there are ways to regain some of the time from trials and FDA application time)
-when the patent is up, others can market your product. These are the generic manufacturers 
-they most go to the FDA and establish that their product is biologically the same as the branded product
-this is done through shorter clinical trials where both the generic and branded drugs are given to patients and monitor the blood levels of the drug are the same then they are biologically the same
-the generic drugs are lower priced as the clinical trials are shorter. This can lower the branded drugs sales
-patents incentives new ideas from companies, and after 20 years, the idea is free to the public and makes the drug better priced.

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