Exam 1

Question 1

History of Drug Discovery

Answer 1

Religious and spiritual healing

Mainly derived from plants

Drug discovery and development based on science only began in late 1880s

Modern pharmaceutical industry began after World War I

Chinese herbal medicine dates back to 3,500 BC

Indian Ayurvedic (herbal) medicine traced back to 3000-
5000 years

Hippocrates is considered the Father of Western Medicine
(400 BC) credited with laying down ethics for physicians.

Question 2

Edward Jenner

Answer 2

1796: successfully experimented with small pox
inoculations, which paved the way for modern vaccines against
infectious diseases.

Question 3

William Withering

Answer 3

1700s: introduced digitalis, a plant extract for

treating cardiovascular diseases

Question 4

John Hunter (Scottish surgeon)

Answer 4

1768: noted scurvy due to the

deficiency of Vitamin C and prescribed lemon juice.

Question 5

Louis Pasteur

Answer 5

1864: discovered microorganisms caused disease

and devised a vaccine against rabies.

Question 6

Alexander Fleming

Answer 6

1928: discovered that Penicillium mold was
active against staphylococcal bacteria. By 1944, large-scale of
penicillin available through the work of Howard Florey and Ernst
Chain.

Question 7

New Chemical Entity (NCE)

Answer 7

1930s: screening natural products then developed synthetic version

Question 8

Recombinant DNA (rDNA) Production

Answer 8

1970s: Biotechnology industry

Fix mutations
Produce more good quality proteins

Question 9

Human-based screening

Answer 9

Medicinal plants

Question 10

Animal-based screening

Answer 10

Anesthetics

Question 11

Bacteria-based screening

Answer 11

Penicillin

Question 12

Tissue-based screening

Answer 12

G protein-coupled receptor

Question 13

Target-based screening

Answer 13

High throughput screening

Function based on structure of compound

Question 14

Mechanism/structure-based

Answer 14

HIV

Question 15

Molecular and Cell based

Answer 15

Kinase inhibitors

Question 16

Genomics-based Patient Profiling

Answer 16

Precision medicine
Personalized medicine

Know molecular aspect of disease
miRNA profiling, RNA sequencing

Question 17

Steps to Modern Drug Discovery

Answer 17

Disease Pathology & Target (know disease and then pathophysiology then which gene or protein is involved)

Target identification

Assay development (quantity invitro with or without cells)

Hit to lead compounds (screen 5,000 compounds to synthesize in test tube; but time is an issue)

Lead Optimization (found compound = 1) toxicity and 2) structural modification to increase potency to make it the best)

Preclinical Development (formulate in tabs, capsules, liquid; close to bring to reality)

Clinical Trials (cells -> small animals -> humans) get approval from FDA and IRB

Question 18

What causes disease?

Answer 18

Bacterial Infection
Host Imbalance

Inhibit overactive proteins (kinase inhibitors)
Replace/substitute underactive protein (insulin)

Which gene is causing the disease?

Question 19

Methods of Drug Discovery

Answer 19

Random untargeted screening

High throughput screening

Molecular modification of known agents (med chem; modify order or functional group of compound or make stable, water soluble, etc)

Mechanism-based drug design (simulations predict binding efficiency then synthesize in the lab to save time and money)

Question 20

New therapeutic model

Answer 20

Sources:

Extraction from plants
Organic synthesis
Animals
Genetic engineering
Gene and cell therapy (stem cells)

Question 21

Preclinical testing

Answer 21

Physiochemical properties
Safety and bio activity (in vitro OR in vivo (ADME))
Preformulation

Question 22

Investigation New Drug Application (IND)

Answer 22

Submission

FDA review

Question 23

Clinical Trials

Answer 23

Phase I
Phase II
Phase III

Question 24

Research and Development

Answer 24

Product formulation
Long-term animal toxicity
Scale up and manufacturing
Package and label design

Question 25

New Drug Application

Answer 25

Submission | FDA review