Chapter 2 (E1) Flashcards
Cost and timeline of drug development/discovery, naming drugs.
A compound that affects physiological functioning once absorbed into the body.
What is a drug?
The cooperative effort of various disciplines to bring a drug from concept to market.
What is drug discovery?
List 3 key individuals involved in the drug discovery process.
1) Molecular biologists
2) Medicinal chemists
3) Lawyers
A general rule of thumb in the drug discovery process is that the profit of { } successful drug(s) must be able to support approximately { } drug(s) in development.
Blank #1) 1
Blank #2) 8.5
What are the main 3 considerations when choosing a profitable disease area?
Choose diseases that are:
1) Highly profitable b/c they affect a lot of people
2) Without current or effective treatment
3) Requiring long-term treatment
What are 2 other strategies to consider when choosing a profitable drug project?
1) “Me too” drugs
2) Finding a new mode of action
What is the purpose of developing “me too” drugs?
To push a similar drug onto the market just b/c there’s enough need and enough patients
What does finding a new mode of action for a drug entail?
Finding a new receptor/enzyme/target
Site of action for a drug that controls a biological response.
What is a target?
What are 3 general examples of drug targets?
Receptors, enzymes, & nucleic acids
Term used describe a promising target.
What is druggable?
How do you determine the structure of a drug target?
X-Ray crystal structure data if available
What is the difference between the “one drug, one target” and “multi-target” approaches to identifying a target?
“One drug, one target” is the traditional approach that can prevent or greatly reduce side effects since the drug only hits one target.
“Multi-target” is the newer approach that hits several targets weakly, and the combined weak responses across multiple pathways could yield a larger biological effect
What is the major pro/up-side to the “multi-target” approach to target selection?
You can hit multiple pathways with a single drug, effectively reducing the amount of medicine required, especially for complex diseases where the pathogenesis depends on a series of simultaneous biochemical events
Method to measure the activity of a compound.
What is an assay?
What are the 3 main types of assays (ordered from least expensive to most expensive)?
1) Biochemical
2) Cellular
3) Animal
The study of { } in biochemical assays is essential to determining how a drug binds to a specific receptor or checking the rate of an enzyme-catalyzed reaction.
Pharmacodynamics
Method of quickly testing a library of hundreds to thousands of compounds for activity against a target via a robot.
What is high-throughput screening (HTS)?
How does high-throughput screening (HTS) of enzymes typically occur in biochemical assays (HINT: Pharmacokinetics)?
Biologists typically follow the reaction profile of the enzyme with and without the drug present via UV-Vis and a plate reader
How does high-throughput screening (HTS) of receptors typically occur in biochemical assays (HINT: there are 2 main methods discussed in lecture)?
1) Tagging drug w/ radioactive isotope
2) Fluorescence assay or UV-Vis
How are compounds chosen for biochemical assays?
A class of molecules is usually known for a target depending on available literature
How many tests are run during a biochemical assay?
As many as needed for all unique compounds, at varying concentrations, duplicated or triplicated
Where or how do we get the compounds needed for biochemical assays (HINT: 3 solutions all involving money)?
1) Synthesize them
2) Merge/buy a company already studying compound of interest
3) Renting out a company
What is the general purpose of cellular assays during assay development?
To see how a compound behaves throughout a whole cell
What is the greatest achievement of a cellular assay that graduates a hit into a lead?
Being able to cross the cell membrane
What model system is used to determine if a drug can pass through the cell membrane? How does this model function?
Caco-2 cells - replicate permeability of intestinal lining
Name 2 other criteria that graduate a hit to a lead.
1) Cytotoxicity
2) Metabolic profile
What is the goal of lead discovery?
To find compounds that show modest activity in biological screenings
What is a possible setback to using genetically engineered cells for cellular assays?
Random mutations
What is the solution to the random mutations within genetically engineered cells found during cellular assays?
Establishing a control compound that works in a non-mutated cell
What is the general purpose of animal assays during assay development?
To begin understanding pharmacokinetics
Biochemical & cellular assays are considered in { } while animal assays are considered in { }.
NOTE: these are Latin phrases
1) Vitro
2) Vivo
This set of studies in lead optimization looks at how structure impacts function.
What are structure-activity relationship (SAR) studies?
A compound that is optimized to show desirable properties.
What is a candidate?
A promising candidate is also known as an NCE or an API. What do these acronyms stand for?
NCE - new chemical entity
API - active pharmaceutical ingredient
What is the purpose of a patent in the pharmaceutical industry, and when is it usually filed?
A legal document that prevents other pharma companies from using compounds described in the patent; patents are filed early into lead optimization
What 4 criteria do preclinical trials assess?
1) Drug safety
2) Side effects
3) Dosing
4) Toxicity
What document has to be filed following preclinical trials?
Investigational new drug (IND)
What is the goal of Phase I of clinical trials? There are 3 criteria studied.
Determining dosage, tolerance, and safety
What is the goal of Phase II of clinical trials? There are 4 criteria studied.
Measuring efficacy, dosing, side effects, and safety
What is the goal of Phase III of clinical trials? There 2 criteria studied.
1) Efficacy over a wider range of demographics
2) Long-term safety
What is the goal of Phase IV or launch? There are 2 criteria studied.
1) Continued efficacy
2) Long-term safety
In this type of clinical trial study, patients don’t know if the drugs they receive are real or placebos.
What is single-blind?
In this type of clinical trial study, patients NOR doctors know if the drugs administered are real or placebos.
What is double-blind?
What is required to re-brand a drug that is already on the market?
A new IND
Why would the fast-tracked/accelerated review of an IND be required?
For diseases that are life-threatening or are in need for immediate treatment
If an IND needs a fast-tracked review, then Phase { } will need to be lengthened.
IV
What type of NDA is required for generic drugs, and when is it filed?
Abbreviated - filed after OG drug patent expires
True or false: Generic drugs are required to have the same API concentration in the body, same dose, quality/purity, intended use, and way of administering as brand-name drugs.
True
Why are generic drugs cheaper than name-brand drugs?
They don’t require all the pre-clinical and clinical trials
What is the purpose of a mass balance study, and what is required for it?
Mass balance studies require a radiolabelled drug administered to a site where it won’t be metabolized to check if the drug properly eliminated in the urine or feces
What is the percent threshold for a valid mass balance study (i.e., how much of the drug must be recovered from waste)?
80%
List the 4 methods of naming pharmaceutical drugs along with relevant associated characteristics of these naming conventions.
1) Chemical identifier - notebook #
2) Chemical name - IUPAC
3) Generic name - contains API, assigned by USAN, approved by WHO
4) Brand name - catchy, determined by linguist, approved by FDA
