Early Stage Drug Discovery and Target Identification Flashcards Preview

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Flashcards in Early Stage Drug Discovery and Target Identification Deck (43):
1

Which activities are considered early stage drug discover?

choosing a disease, identifying and validating a target

2

what is involved in lead compound identification?

in vitro bioassays and compound screening

3

what happens after lead compound identification?

lead optimization

4

what happens after lead optimization?

preclinical in vivo studies

5

how long does the discovery/ preclinical phase of the drug discovery pipeline take?

3-6 years

6

how long is the clinical phase of drug discovery?

6-7 years

7

how long does it take and how much does it cost to discover a drug?

10-15 years, ~1 billion dollars

8

an orphan drug treats a disease/disorder that affects _____ people in the US

less than 200,000

9

orphan drug designation means:

government grants for development, tax breaks on clinical study costs, extended market exclusivity

10

antifungals take advantage of _____ in ___ between fungi and humans

significant structural differences/ dihydrofolate reductase

11

genomics

comparison of genomic DNA levels and markers

12

transcriptomics

comparison of mRNA levels and markers

13

proteomics

comparison of total protein levels and markers

14

metabonomics

comparison of levels of cellular metabolites

15

post-genomic target identification: ___, ___, ___, ___, ___

target ID/ target validation/ assay development/ screen for active compounds/ drug development

16

if you have a compound with interesting biological activity and you want to know how it works use

affinity purification (Biotin/Avidin) and bioinformatics

17

if you only have a disease state of interest and you want to know what the potential drug targets are in your model

use genomics (microarrays), proteomics (activity-based protein profiling), and bioinformatics

18

biotin: vitamin _ or vitamin _

H/ B7

19

biotin is _________ for __________ in ______

an enzyme cofactor/ carbon dioxide transfer/ numerous carboxylase enzymes

20

biotin plays an integral role in _______

fatty acid synthesis and catabolism

21

avidin is a ___________ found in egg whites

homotetrameric protein

22

the Kd for avidin/biotin affinity is ___. Normal non-covalet binding interactions in water are in the ________ range

~10^-15 M/ 10^-1-10^-6 M

23

what is the first step of affinity purification?

biotinylate the lead compound. This conjugates structure binds to immobilized avidin

24

after the ligand of interest is attached to immobilized avidin...

cell lysate is added to the column

25

after cell lysate is added to the column in affinity purification...

non-binding proteins are eluted

26

after non-binding proteins are eluted...

free ligand is washed through, eluting the bound protein

27

affinity purification protocol gives you

the protein that binds to your ligand of interest

28

bioinformatics:

the generation of databases and application of computer algorithms to better understand molecular biology

29

________ is a database of 3D protein structures. You can input _______- an it will generate _____-

Target Fishing Dock/ small molecule structures/ potential binding partners based on energy conformations

30

___ is created from ___ using ___ and it contains ______

cDNA/ mRNA/ reverse transcriptase/ no introns

31

how many copies of cDNA can PCR produce in 2 hours

millions

32

genomics approach to target ID:

identify novel disease targets at the level of gene expression by comparing normal and diseased tissues

33

when using a proteomic approach to Target ID you use ________ on your protein sample. The you excise and ____ protein from ______. Then you use ___________ analysis.

two dimensional separation by isoelectricfocusing and SDS-PAGE/ digest protein/ gel/ mass spectroscopy

34

there can be ____ issues with proteomics due to _________ or _______ proteins

purification/ membrane-associated/ highly charged

35

how do you amplify protein for proteomics

you don't

36

__________ can cause issues with proteomics

post-translational modifications

37

activity-based protein profiling (ABPP) uses

active site-directed probes labeled with a fluorophore or biotin to profile the functional state of enzymes in whole proteomes

38

gene ontology:

bioinformatics initiative to unify representation of genes and gene products across all species

39

cellular component of gene product classification:

where is the protein located?

40

molecular function of gene product classification:

what does it do, individually?

41

biological process of gene product classification:

what does it do, globally?

42

gene ontology in Target ID is a companion to _______ and gives data on ________

microarray analysis/ up or down regulated genes

43

______ predicts 3D structure from gene sequence

Potential Drug Target Database