Methods and principles

Question 1

E. Small molecule kinase inhibitors

Answer 1

Gleevac
Tasigna

Question 1

E. Chemotherapeutic drugs

Answer 1

Taxol
Velban

Question 2

Treatments of Cardiovascular diseases

Answer 2

Treat Hypertension:
Diuretics
Beta-blockers
Angiotensin-converting enzyme (ACE) inhibitors

Question 3

E.Diuretics

Answer 3

Midamor

Question 4

E. Beta-Bockers

Answer 4

Tenoretic

Question 5

E. ACE inhibitiors

Answer 5

(Angiotensin-converting enzyme)
Capoten

Question 6

Statins

Answer 6

Block cholestral production

Question 7

E. Statins

Answer 7

Lipitor
Zocor

Question 8

Alzheimer’s

Answer 8

-form of dementia
-no treatment/ only delay side effects

Question 9

potential targets of Alzheimers

Answer 9

-Beta-Secretase (BACE)
-Gamma-secretase
-Glycogen synthase kinase 3 beta
-Cyclin-dependant kinase 5

Question 10

chalenges with antibiotics

Answer 10

Bacteria mutate and become resistant over time
-EG. MRSA became resistant to methicillin
drug discovery must be a continuous process that can never end

Question 11

challenges with drug discovery process

Answer 11

-Understand disease or infectious agent biology
-Toxicity to normal cells
-Physiological effects
-Safe delivery
-Which compounds would pharma like
-Cost of development

Question 12

Stages of Drug discovery

Answer 12

discovery
-Target discovery
-lead discovery
-Lead optimisation
Development
-Pre-clinical
-proof of concept
-Full development
-Registration/launch

Question 13

Problem with Plumbagin

Answer 13

-Too toxic
-Has too many off-target effects

Question 14

Contributors to target selection

Answer 14

-financial profit
-Viable drug target
-compound has off-target effects
-Pharmokinetic issues
-Rare diseases

Question 15

SSRI

Answer 15

selective serotonin reuptake inhibitors
-Treat neurological disorders

Question 16

E. SSRI

Answer 16

Zolofot
Zelmid
Celexa

Question 17

Limitations of physical HTS

Answer 17

-Sensitivity (False positives) and specificty (False negatives)
-Sample degradation
Requires repetition

Question 18

limitations of virtual HTS

Answer 18

• Results are only predictions and arent real
  -Requires validation in labratory
  -the proteins structures are developed through X crystallography but in real life, biological molecules are either dissolved or membrane bound

Question 19

Lead optimisation book

Answer 19

learn garph

Question 20

what is the main objective of lead optimisation

Answer 20

-To continuosly change the molecules structure until it has greatest possible structure

Question 21

NB qualities for clinical candidate

Answer 21

-Active
-Selective
-Novel
-PK
-Stable
-Safe
-Soluble

Question 22

Screening cascade

Answer 22

objective is to dectease number of compounds at each level
Primary screening assay
1- Determine low dose (if compounds are active enough to warrant investigation)
2-determine selectivity and physiochemical properties (see if it interferes with other systems)
(over 70 ion channels similar to Kv.15)
Secondary screening assay
3-risk of side effects
4-ADME: absorption, distribution, metabolism, extraction ( must be druglike like have high aqueous solubility)
potent, selective, BBB, cant be metabolized too fast
5-PK (pharmokinetic properties) distribution (freely distributed or confined to an organ/ How rapidly is compound excreted or metabolised)
6-In vivo testing and safety studies (animal studies)