Lecture 4

Question 0

HTS

Answer 0

Rapid ID of lead compounds for early phase drug discovery

Question 1

Complications with drugs based on adrenaline?

Answer 1

Catechol unit is easily oxidized

Non-selective and interacts with multiple receptors

Question 2

HTS requires?

Answer 2

Viable target to screen against
A biological assay and necessary automated equipment
A source of compounds

Question 3

SPA

Answer 3

ID compounds that bind to target of interest

Strength of binding is proportional to the amount of luminescence emitted

Question 4

Disadvantages to SPA

Answer 4

Radioactive
Long read times
Susceptible to non-specific binders
No applicable to all targets

Question 5

FLIPR-HT

Answer 5

Determine whether an receptor binding is an agonist antagonist or inverse agonist

Question 6

HTS setup

Answer 6

Compound selection
Compound collection
Chemical space
Human and pathogen genomes
Target ID
Validate/tractable targets
HTS development

Question 7

Compound library projects have what targets of interest?

Answer 7

G protein coupled receptors, ion channels, protease enzyme inhibitors, kinase enzyme inhibitors

Question 8

Combinatorial chemistry

Answer 8

Building a library
Easy to remove impurities and wash to get pure compound
Very difficult to be efficient and to analyze

Question 9

CombiChem

Answer 9

Allows synthesis of more than one compound at a time

Question 10

Solid-phase Organic Synthesis

Answer 10

Polystyrene + Linker + FG 
➡️add substrate➡️ 
\+ substrate 
➡️reaction➡️ 
- substrate + product 
➡️washing➡️
Purer product
➡️detachment/filtration➡️
- product leaves Polystyrene + Linker + FG