Introduction into drug discovery

Question 1

What is a drug?

Answer 1

A drug is any substance that causes a physiological change in the body.

Question 2

Name four natural products with a pharmacological effect.

Answer 2

1. coal tar
2. fermentation broths (Brühe)
3. plant extract
4. animal fluids

Question 3

What are the disadvantages of peptides as drugs?

Answer 3

Peptides are not stable in the human body because of proteases.

Question 4

What are peptidomimetics?

Answer 4

Peptidomimetics are modified peptides in which the peptide bond is replaced by a more stable bond.

Question 5

How are peptidomimetics also called?

Answer 5

Protein epitope mimetics (PEMs)

Question 6

Name one example for whole proteins which are used as drugs.

Answer 6

Antibodies

Question 7

What is Atorvastadin (Lipitor) ?

Answer 7

• Statin, used for the lowering of LDL and cholesterol
• Drug for the treatment of cardiovascular diseases

Question 8

How is Atorvastadin (Lipitor) working ?

Answer 8

• Competitive inhibitor of HMG-CoA reductase
• Controlling of the hepatic cholesterol production
• Lowering LDL and cholesterol

Question 9

What is Infliximab (Remicade) ?

Answer 9

• Mouse/human monoclonal antibody
• TNF inhibitor
• Leads to the suppression of the immune response

Question 10

What is Adalimumab (Humira)

Answer 10

• Human monoclonal antibody
• TNF inhibitor
• Leads to the suppression of the immune response

Question 11

What is Rituximab (Rituxan)?

Answer 11

• Drug for the treatment of diseases characterized by too many or dysfunctional B cells
• Destroys normal malignant B cells

Question 12

What is Harvoni ?

Answer 12

• Drug to cure people infected with hepatitis C
• Combination of ledipasvir and sofosbuvir

Question 13

What is the function of ledipasvir?

Answer 13

It decreases the activity of NS5A.

Question 14

What is the function of sofosbuvir ?

Answer 14

It decreases the activity of NS5B.

Question 15

What is Gleevec ?

Answer 15

It is a drug for the treatment of chronic myeloid leukemia (CML) and acute lymphocytic leukemia

Question 16

How does Gleevec work ?

Answer 16

• It blocks the ATP-binding site of the bcr-abl tyrosine kinase
• The activity of this kinase is associated with cancer

Question 17

What is the philadelphia chromosome ?

Answer 17

• Translocation between chromosome 9 and 22
• Leads to the expression of an oncogenic bcr-abl fusion protein
  -> unregulated tyrosine kinase
• Associated with chronic myeloid leukemia (CML)

Question 18

What is Viagra ?

Answer 18

• A drug which was originally inteded as a treatment for hypertension (high blood pressure)
• Nowadays used as a treatment for erectile dysfunction

Question 19

How does Viagra work ?

Answer 19

It blocks the cGMP-binding site of cGMP-specific phosphodiesterase 5 (PDE5)

Question 20

What is Taxol ?

Answer 20

• Treatment for ovarian and breast cancer
• Originally found in Pacific Yew Trees

Question 21

How does Taxol work ?

Answer 21

• Stabilisation of the microtubules
• Down-regulation of cell division

Question 22

Why is Insulin an atypical drug ?

Answer 22

• It is injected as a crystalline suspension
• This atypical aggregate state ensures greater stability and more even absorption of the insulin

Question 23

Name two pharmacological agents originating from plants, the benefits and the corresponding plant.

Answer 23

1. Cardiac glucosides
   -> Occurs in foxglove
   -> Treatment for circulatory problems
2. Salicylates
   -> Occurs in willow bark
   -> Is the active ingredient in aspirin
   -> Acts as a COX inhibitor against pain and inflammation

Question 24

What was Paul Ehrlich’s original profession?

Answer 24

• Organic chemist in the dye industry
• Development of dyes from coal tar

Question 25

Paul Ehrlich proposed the basic mechanism of chemotherapy. What was meant by this ?

Answer 25

- He hypothesized that various cell types contain different chemoreceptors that bind certain molecules - This differential binding could be used to cure diseases

Question 26

At the beginning of the 20th century, Paul Ehrlich revolutionised the approach to medical research in two respects. What were they?

Answer 26

1. Research by an interdisciplinary team 2. Investigation of new drugs in animal studies

Question 27

Against which disease did Paul Ehrlich develop a drug in 1909 that became the first modern chemotherapeutic agent?

Answer 27

Syphilis

Question 28

Paul Ehrlich discovered the basics for the concept of produgs. What is this concept ?

Answer 28

- Prodrugs are inactive compounds that are converted by the metabolism into active drugs inside the body - Absorption and distribution can be improved - Side effects can be reduced

Question 29

What was the first broad-spectrum antibiotic ?

Answer 29

- Prontosil - Discovered in 1935

Question 30

Prontosil is a prodrug. What is the active metabolite ?

Answer 30

Sulfanilamide

Question 31

Name three types of diseases which are treated with sulfanilamides ?

Answer 31

1. Bacterial infections 2. Diabetes 3. Hypertension

Question 32

Name three pharmacological agents which were discovered/synthesized for one indication and then turn out to be useful for others.

Answer 32

1. Salvaran -> Was intended as a treatment for sleeping sickness, was useful for the treatment of syphilis 2. Viagra -> Was intended as a treatment for hypertension, was useful for the treatment of erectile diyfunction 3. Tamoxifen -> Was intended for birth control, was useful for the treatment of cancer