Medicinal Chemistry: The Basis of Drug Discovery

This week was about enzymes and I felt glad because in AP Biology proteins were a hard unit, but enzymes were easier. Enzymes are interesting because of the graphs and conceptuality of them makes them easier on my brain. Being able to keep track of the different inhibitors might be tricky, and using the equations may also be hard My question is do researchers have models and have to decide if it fits that way? Is it more trial and error?

When analyzing medicinal chemistry, one must talk about enzymes. The purpose of an enzyme is to speed up reactions in the body, allowing certain process to continue. Most people know that enzymes aid in the chewing and digestive process, however enzymes can be found in most cells. Enzymes have an active site, which is where the molecules attach to react. Inhibitor are molecules that stop enzymes from working. These can be man made or made by the body. When a body produces hormones, a inhibitor is usually released to prevent an excess of hormones. The main type of inhibitor is a competitive inhibitor. A competitive inhibitor links to the active site, preventing what is supposed to go there from getting there. Most medicines targets enzymes, because the process it is supposed to be doing is halted or at least intensely slowed. The reason competitive inhibitors are the most popular in medicine is because the active site of a specific enzymes is unique, and the shape requir...

Video 1 -Enzymes are a specific type of protein   -Enzymes are the potential targets of drugs -Enzymes are catalysts for the reactions they facilitate   -an enzyme+substrate yields and enzyme substrate. That is a reversible reaction -the enzyme substrate can turn to enzyme + product when the product is released -rate substrate concentration graph   -V max is a theoretical maximum that requires infinite concentration of substrate -as substrate concentration increases, the rare increases in a logarithmic fashion -1/2 V Max is a special value. Concentration required to get 1/2 Vmax is called the michaelis constant   -michaelis constant is a concentration   -V=(Vmax•[S])/Km+[S] -called michaelis-menten equation.   -it's a hyperbolic shape -difficult to match data to function bc in early 1900s didn't have data software -a linear equation was needed -1/V=(Km/Vmax)•(1/[S])+(1/ Vmax) -this is a linear equation that uses reciprocal...

When i was learning about the complexity of proteins and drugs targeting proteins my reaction was that of surprise. I had no idea that the system of proteins in the body was so complex, and after taking AP Biology I still didn't have a very understanding about proteins. The video in the class were very helpful and through a website 3D model made me see exactly what the levels of structure are. My question for this week is how they pick proteins to target? Is there a certain structure they are looking for? this seems like a very complex career and one that goes unrecognized.

Understanding what proteins are is critical to being able to identify the protein pathways to target with a drug to disrupt the disease. Proteins are made up of amino acids bound together. They are unique not only in which amino acids makes them up, but also how the have folded into structures, and how those structures has folded. Some proteins also only work when folded with another protein. Proteins are very complex, and the amount of different proteins are vast. When a drug targets a specific protein, they are looking to interrupt its purpose and with that disrupt the disease. This is usually done by either blocking the binding location with a molecule, or making an inhibitor that will stop the production of whatever that protein is doing. The way the drugs that are developed requires a deep understanding of proteins and protein structure. The chemistry involved in designing molecules to have very specific properties, and the biology to determine which proteins to target is immens...

Video 1 -proteins are made up of amino acids, and how the amino acids are structured -amino acids has a carboxyl group(COOH) and an NH2 group   -if the NH2 group is in the alpha position, it is an alpha amino acid -also attached to the alpha carbon is an "r" group, which can very -the "r" group determines which amino acid it is. -the r group can go from simple (H) to complex organic compounds even with benzene rings -amino acids make up proteins by linking together -the bond is called an amide linkage, and is the backbone for the R groups can stick out and be unique -the differences in the r groups make all the different proteins in the body -primary structure is the order of the amino acids in the chain   -use protein data bank for information   -the backbone bends with the different amino acids   -even small proteins are very complex -secondary structure is regions of localized folding in the backbone ex. alpha helices, can be right or...

My reaction to the way drugs are discovered and developed is mainly of interest. The science part and the business parts are both very interesting. knowing about the long and difficult process makes me understand why drugs aren't being discovered all the time, and also why people like Martin Shkreli who are CEOs of these companies can raise the price of their drugs so much and still have sales. this is because when a new drug is discovered, the government rewars you with market exclusivity, and if your drug is the only drug that will save someones life you can charge whatever you want as euthanasia is illegal, and doctors must always save a patient. I'm curious about how exactly the testing is done, and how through it really is. I'm also curious on the business side about how much is the patent system really necessary because of how much it hurts people who need the drugs. would drug companies still make new drugs without the patent system?

The path of an idea about a disease that needs a cure, to a drug available on the market is long and complex. There are two approaches that are mainly used. The first is Target Based Drug Discovery, which takes a protein to target that is chosen by Molecular biologists which is important to a disease and how it works.then after testing 10,000s to over a million molecules for their ability to bind to the protein and other factors like how well it can move through a cell or how well it can be patented. you then have a lead, which you test on animals to test toxicity. Then, the FDA will approve it if everything is correct, which is permission to begin clinical trials on humans. Clinical trials are done in three phases: phase 1 is a small group of healthy volunteers only to test the drugs toxicity and safety, phase 2 is done on a bigger group of patients with the disease mainly to test dosage, efficacy, and safety, and phase 3 done on an even bigger group of people to test the drugs effect...

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 looki...

I was surprised as to how recent the FDA is and how new of a field medicine really is. I was sad to learn but not surprised that it took the death of over 100 kids to make the USA decide it was time to start regulating medicine. I am realizing how much chemistry really does interest me because as I learn about the structure and formation of medicine I want to continue learning more. I was surprised to learn about the drugs and their structure so early but I was glad to learn about a wide range of types of drugs. A question I have is what is considered unsafe and what is allowed? How many liver failures can you have with it still be considered safe? In the advertisements for drugs they list some pretty serious thing as side effects, I've always wondered how is that safe?

The history of medicine before the 1938 Food, Drug, and Cosmetic Act was full of new breakthroughs but also a lot of untested drugs. The history of drugs begins with ancient China 5,000 years ago, when people made a tea with a specific type of shrub that was later found to contain Ephedrine. Ephedrine is a anti cough medicine that is still used today. Its diastereomer Pseudoephedrine (Sudafed) is over-the-counter, however, because it can be used to make methamphetamines one must show a license. All of the drugs that have been mentioned are a part of the same class of drugs, or have the same pharmacophore. They are all Phenethylamines, which means they all have the sane basic structure as each other therefore all have similar effects, just at different effectiveness. The creation of the FDA was a response to the Elixer Sulfanilamide tragedy. In 1937 a company was trying to market a drug to kids by making the liquid it was mixed into sweet. This comapany decided to use a chemical cal...

Post 1 week 1 Pre-regulatory Drugs -First use of medicine goes back 5000 years with an herbal tea which turns out to have Ephedrine, a stimulant and anti cough medicine. -Ephedrine is an Alkaloid which means it comes from nature, has a basic Nitrogen atom, and some complexity -The Pharmacophore of Ephedrine is Phenethylamine which means it has a benzene ring, a two carbon bridge, and a Nitrogen atom. -Pharmacophore is the division of drugs into their most basic structure -Pseudoephedrine (Sudafed) is another example of a phenethylamine, along with Methamphetamine and fenfluramine. -Fenfluamine was a diet pill because all phenethylamines make you feel like you have energy without having to eat, however also caused heart damage -Adverse Effects are effects of something that are worse then what you are trying to cure and would cause someone to not want to take the drug -Side effects are other things that could happen that would only at most be a minor inconvenience -Off labe...