Lecture 2

Question 1

agonist and antagnonists

Answer 1

agonists bind to target and cause a pharmacological response, antagonists bind to a target and DO NOT cause a pharm. response

Question 2

target validation

Answer 2

proving the target is directly involved in the disease process through testing after basic research

Question 3

high-throughput screening (HTS)

Answer 3

screening for target-compund interaction provides real results used in drug discocery, time consuming and expensive

Question 4

Virtual screening (VS) in silic

Answer 4

computational technique to simulate screening, lower cost, no chemical synthesis , large chemical databases, cannt substitute real in virtro screening

Question 5

how to choose a lead (Lipinski’s rule of 5)

Answer 5

looking for drug like properties: ADME- absorption, distibution, metabolism,and excretion
elements important for oral drugs include: charge, size, lipid solubility
-does not predict if drug is pharmacologically active

Question 6

Selectivity Index (SI)

Answer 6

determines potency of a drug
SI=CC50/EC50
cytotoxic concentration that kills 50% health cells / concentration causes 50% of maximum effect
ideally: high concentration needed to kill 50% drugs
low concentration needed for biological effect
a higher SI ratio number indicates a safer and more effective drug

Question 7

lead properties

Answer 7

ADME, oral bioavailability in rat, potency in cell based assay, selectivity index >100, good physiochemical properties (aqeuous solube and chemical stability)

Question 8

lead optimization

Answer 8

structursal modification of biologically active compound to: improve potency,reduceoff target effects, optimize ADME

Question 9

drug potency

Answer 9

acitivty of a drug needed to produce a defined bioloical effect expressed in concentration

Question 10

pharmacophore

Answer 10

set of structural features in molecule recgonized at receptor site ad essential for biological avtivity
includes chemical functional groups, their position and spatial orientation
must be preserved during lead optimization

Question 11

Varenicline (Champix)

Answer 11

smoing cessation drug acts a partial agonist of nicotinic receptor, therefore produce dopamine but additional smoking does not increase the effects ofdoamine, ierelaxationor happiness