Screening Flashcards
What’s the purpose of in vitro inhibition testing?
to test drug lead candidates quickly, to determine potency of identified hits, the affinity to the target protein and the mode of action
When testing drug candidates the main challenge is to find the best balance between which 2 factors?
sufficient activity against desired target and minimal activity against any other targets to reduce off-target effect
Describe 4 types of drug tests
in vitro (target molecule, whole cells, isolated tissues or organs), in vivo (living systems such as animals or human volunteers) , testing antibacterial agents on microbiological cultures (considered in vitro) and assessment of an antibacterial agent which involves infecting a test animal with bacterial strain then giving the same agent to animal to inspect its efficacy (considered in vivo)
What is the purpose of performing enzyme inhibition assays?
to quantify the inhibition properties of the identified hit compounds against selected enzyme
How would you conduct an enzyme inhibition assay?
hit compound added to assay mixture and inhibition potential can be evaluated by comparing the enzyme activity in the presence and absence of the inhibitor
Give an advantage of enzyme inhibition assays
you can run multiple independent experiments at the same time
Explain the difference between affinity, efficacy and potency
affinity is the strength at high compounds bind to receptor, efficacy is the measure of max biochemical effect resulting from the binding and potency is the concentration of the agonist required to produce half of the max possible effect
What is high throughput screening?
it’s an automated type of in vitro testing, it’s carried out on a small scale but can be carried out on large numbers of compounds in a short time. It’s designed to identify a drug lead within a library of candidate molecules
What are the limitations of in vitro tests?
they don’t evaluate the ability of a drug to reach target. Don’t demonstrate a physiological or clinical effect, don’t identify side effects or effective prodrugs
Purpose of in vitro tests + an advantage
to measure the interaction of the drug with the target, can also be used to test for pharmacokinetic properties of drug candidates – results easier to rationalize as less factors involved
Purpose of in vivo tests + a disadvantage
measures an observed physiological effect, measures a drug’s ability to reach biological target and interact with it, can identify possible side effects – rationalizing results more difficult due to large numbers of factors involved
What is the therapeutic ratio/index?
it compares the dose level of a drug required to produce the desired effect in half the test sample to the dose that is lethal to half the test sample
