Drugs Discovery, development and approval Flashcards
________- protects public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines, and other biological products for human use
FDA
New Drugs at FDA goes thru ______________(CDER)
Supports the pharmaceutical industry at every step of the process
FDA’s Center for Drug Evaluation and Research
What are the 5 different phases of early-stage discovery?
Target ID and Validation
Hit Identification
Lead Optimization
Efficacy and Safety
Development Feasibility
What are the two different approaches represented by the two different starting points in the drug discovery cycle?
Advantages and disadvantages for both
Indirect pathway
DisAdvantages: Needle in a haystack, can get false positive
Direct pathways
Advantages: rational design approach, use previous knowledge of the ligand and protein to figure our a design fro the drug
Choose the best option
(Chemical (NMEs) / Biological Products (BLAs) )
Made by chemical synthesis
Small simple, low molecular weight
Easy to characterize and purify
Chemical (NMEs)
Choose the best option
(Chemical (NMEs) / Biological Products (BLAs) )
Biological synthesis using human DNA segments, bacterial or animal cell lines
Large, heterogeneous, high molecular weight proteins
Feasible labile structure
Difficult to characterize and purify
Complex manufacturing process
Biological prodcuts
True or False
All of these statements relate to Antibody Diversity which is the major class of BLAs
______Before any exposure to a foreign substance, humans do not have any antibody molecules
_____ Diversity is generated by somatic rearrangement of gene segments in B cells
__ B Cell DNA is similar to Germ-line DNA and DNA from other somatic cells
____ Monospecilic allelic exclusion results in only one heavy and one light chain gene being expressed in each B cell, which makes an antibody and can make a million copies.
______ Secondary antibody reporters in response to a foreign substance
False, Humans can make 10^15 different antibody molecules
True
False, B Cell DNA differ from Germ-Line and other somatic cells DNA
True
True
What is affinity maturation?
Hint: look at the image
Antibodies undergo somatic hypermutation, point mutations in heavy and light chain variable regions that occur 1 mutation/generation in stimulated B cells
B cells in which mutations have produced higher affinity antibodies are selected for the antibody
What is a monoclonal antibody?
What are the advantages of monoclonal antibody over convalescent plasma or serum?
Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses.
As shown in the image, the B lymphocytes die after a few days in culture. And the mutant cell line derived from a tumor of B lymphocytes cell grow indefinity,
Anti-COVID 19 Develop Monoclonal Antibody Cocktail __________
This Treatment:
Reduces the severity of symptoms and helps eliminate the virus in infected patients
If given to people who are not affected will prevent the infection
REGEN-COv2
What is cystic fibrosis?
It is an inherited disease that results in LOF mutations in CFTR, a protein that helps maintain the balance of salt and water.
Can affect the mucus that is in our lungs, make it very thick and sticky leading to difficulty breathing and increase infections from diseases
What are the impacts of mutations in classes? All these classes will impact the Cl- cell current.
Where can you find the most common CF mutation?
Class VI
Class III
Class II
Class I
Class IV: reduces i
Classes III: reduced Po
Class II reduced n via trafficking
The most common CF mutation delta F508 is in Class II
Class I reduce n via transcription/translation
Choose out of these three drugs which would work best for these individuals?
(Kalydeco/Lumacaftor/Orkambi)
Hornsby(Patient) comes in with the mutation class III, reduces Po.
Would give Hornsby
Kalyedeco
Sprocket came in with the most common CF mutation (delta F 508 in Class II) and you gave him Kalydeco but it had no effect and Sprocket continues to have breathing difficulties. What can you conclude from this?
Sprocket has very few copies of CFTR in the plasma membranes, so Kalydeco does not have enough copies of CFTR to work with to increase Po alone. So it won’t give a large amount of Chloride current to restore the lungs.
(Look at the first one on this graph)
Choose out of these three drugs which would work best for these individuals?
(Kalydeco/Lumacaftor/Orkambi)
Hazel comes in with the most common CF mutation (delta F508) in Class II.
Lumacaftor
