Drug Discovery and Development One Flashcards Preview

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Flashcards in Drug Discovery and Development One Deck (29)
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1
Q

Whats a general overview of the drug development pathway?

A
  • Early stage research and discovery
  • Preclinical studies
  • Phase 1-3 clinical studies
  • FDA review and approval
2
Q

What does early stage research and discovery encompass?

A
  • Target ID
  • HIT discovery
  • Lead Generation
3
Q

What does target ID involve?

A
  • Phenotypic screen
  • HIT discovery
  • Target ID
4
Q

What are two types of screening for drug discovery?

A
  • Target Based (knowledge of drug, choose targets to test)

- Phenotypic (test lots of receptors for effect)

5
Q

Whats the advantages for target based screening of drugs?

A

Advantages:

  • Application of molecular and chemical knowledge
  • Small molecule screening strategy
  • Biological development (i.e antibodies)
6
Q

Whats the disadvantages for target based screening of drugs?

A

Disadvantages:

  • Target might not be relevant to disease
  • No therapeutic index
7
Q

Whats the advantages of phenotypic based screening?

A
  • Does not require knowledge of MOA

- More effective translation from assay to therapeutic impact

8
Q

What are the disadvantages of phenotypic based screening?

A
  • Optimizing properties with MOA knowledge

- Lower throughput than target based

9
Q

In target based screening, what are some targets used?

A
  • Ligand binding site
  • Catalytic site (enzymes)
  • Allosteric site
  • Protein-protein interface
  • Protein-membrane interactions
10
Q

In target based screening how do we develop drugs?

A
  • Makes molecules related to the known ligands (analogues)

or

  • Screen for knew molecules based on the receptors and known ligand properties
11
Q

In classical pharmacology, how are receptors classified?

A

Receptors were classified based on their ligand response profile

(classification could lead directly to new therapies)

12
Q

Are ligands only recognized by one protein?

A

Different proteins can recognize the same ligand

13
Q

Whats an example were drugs were developed based on being analogues to the known ligand?

A
  • Adrenalin acts on adrenoreceptors
  • Use antagonism for angina
  • Use agonism for asthma
14
Q

How is angina treated?

A

Use of propanalol as an antagonist at the b-receptor to decrease its heart rate, thus decreasing the work its performing/oxygen needs

  • Doesnt affect contractile state
15
Q

How are disease states used to develop drugs?

A

Critical evaluation of disease data generates a hypothesis about what is needed from a drug

16
Q

What is a HIT discovery?

A

When the target phenotype is affected by a compound

17
Q

During the development of propanolol, what pathway of analogues was unsuccessful?

A

Symmetrical analgoues

18
Q

What is lead development?

A

Using a compound that is known to have the same affect (agonist, antagonist etc) as you want, and then looking into analogue structures (produce precise effect)

19
Q

What was the inertial treatment for asthma?.

A

Adrenalin

20
Q

Why was Adrenalin no longer used to treat asthma?

A

Caused hypertension, tachycardia etc as acted on all receptors

21
Q

What was the current treatments for asthma based off?

A

Adrenalin analogues

22
Q

What must be done in analogue envelopment?

A
  • Toxicity and metabolic profiles must be developed
23
Q

What is currently used to treat asthma?

A

Sulbutamol

24
Q

Why is sulbutamol used?

A
B2 AR selective
Fast Onset
Longer acting than isoprenaline
Weaker binding
Best results by inhalation
25
Q

Do different agonists stabilize different conformations of the activated receptor-binding pocket?

A

Protein bind to the ligand i.e protein changes shape not the ligand

26
Q

Are chemical properties useful in discovery?

A

Yes, but must refine exactly what you are looking for

27
Q

How can screening assays be clouded?

A

Interference of compounds inc:

  • Optical interference
  • Reactions
  • Aggregates
  • Pan Assay Interference Compounds (PAIN)
28
Q

How can you prevent screening assays from being clouded?

A
  • Known problem compounds can be filtered out based on substrucure
29
Q

When you develop a library of known drug information, whats important about someone using it?

A

It will be context dependent

i.e Might say a drug doesnt work (but drug was tested under oral admin, when IV it works)