Drug targets - Helgi Flashcards
1
Q
paracrines and autocrines
A
- local communication signal
- chemicals diffuse to target
- example: cytokines
- autocrine: receptor on the same cell
- paracrine: receptor on neighbouring cells
2
Q
receptor locations and implications for their ligands and targets
cyotosolic or nuclear receptors
A
- lipophilic ligand enters cell
- often activates gene
- slower response
2
Q
Stuff that FDA will generally want you to do
A
- Develop a pharmacological profile of the drug
- determine the acute toxicity of the drug in at least two species of animals
- conduct short-term toxicity studies ranging from 2 weeks to 3 months, depending on the proposed duration of use of the substance in the proposed clinical studies
3
Q
Types of ion channels
A
- voltage-gated channels (VGIC)
- na+ channel
- ca2+ channel
- k+ channel
- Cl- channel
- ligand-gated channels
- NT receptor
- ca-activated K+ channels
- cyclic nucleotide gated channels (CNG)
3
Q
Different transmitter (ligand) gated ion channels
A
- Nicotinic ACh
- 5-HT3
- GABA-A
- Glycine
- Glutamate
- AMPA
- NMDA
- Kainate
–> All (?) form pentamers, usually heteropentamers
3
Q
Hormones
A
- long distance communication
- signal chemicals made in endocrine cells
- transported via blood
- receptors on target cells
3
Q
neurons and neurohormones
A
- long distance communication
- neurons: electrical signal down axon signal molecule (NT) to target cell
- neurohormones: chemical and electrical signals down axon hormone transported via blood to target
4
Q
Conventional drugs act on
A
- enzymes
- carriers/transporters
- ion channels
- receptors
5
Q
Non-clinical tests assess
A
- toxicology
- pharmacology
- metabolism
- bioanalysis
- pharmaceutical analysis
- biosafety
7
Q
the insulin receptor cascade
A
- absence of insulin - tyrosine kinase is inactive
- binding causes a conformational change
- activated tyrosine kinase transfers phosphate group to:
- specific tyrosines of alternate subunit –> autophosphorylation
- a soluble protein substrate (family) –> insulin receptor substrates (IRSs)
8
Q
Information included for the FDA meeting at end of phase II
A
- data supporting the claim of the new drug product
- chemistry data
- animal data
- proposed additional animal data
- results of phase I and II studies
- statistical methods being used
- specific protocols for phase III
- copy of the proposed labeling for the drug
10
Q
Four main groups coupled to effector systems
A
- ligand-gated channel: ligand opens or closes the channel
- receptor enzymes: ligand binding activates an intracellular enzyme
- G protein-coupled: ligand binding opens an ion channel or alters enzyme activity
- nuclear receptors
12
Q
receptor enzymes
A
Signal molecule binds –> tyrosine kinase on cytoplasmic side –> phosphorylates protein
13
Q
Ligand binding to integrin receptors
A
… alters the cytoskeleton
15
Q
Actions of signal molecules
Calcium
A
- Calcium
- muscle contraction
- channel opening
- enzyme activation
- vesicle exocytosis
