Drug Design Flashcards
gene therapy work by:
having a vector carrying a new gene into the cell. The gene will replace something that is missing or damaged.
Example disease tx that gene therapy is use:
Cystic fibrosis
Cystic fibrosis is
a genetic disorder that lead to mutant receptors production. (inability to transport chloride from the airway lumen into the airway epithelial cells –>bc of the mutant receptor)
Gene therapy working for cystic fibrosis by
deliverying new receptor gene via nasal spray to be taken up by the airway epithelial cells to make functionnal chloride channels.
Microarray technology is use to
determine which genes of the genome are expressed in diff tissues under diff. circumstances.
Bioinformatics is
use to get info we need by looking at thousands of situations/samples.
Steps DRUG DISCOVERY:
- Compare tumour with normal cells. (gene they express and protein)
- Info obtain provide insights about novels molecular targets.
- Target validation (to know if it is useful at the end)
Stage in drug design:
- Drug discovery
- preclinical
- clinical trials
- FDA review
- Clinic
In preclinical studies we use
combinatory chemistry
Lead optimization is
the improvement of the lead compound base on animals and cells studies.
High throughput screening is?
done by?
put enourmous amount of compounds through the screening test. (mass screening)
Done by robots.
2 types of assays
Cell-free assays (ligands-receptor interactions.)
Cell-based assays (receptor gene expression or sec messenger.)
High throughput screening cannot evaluate:
Bioavailability Pharmacokinetics Toxicity Mutagenicity Specificity*
Subcellular fraction is use for?
testing drugs candidates (spectrometry..)
Computational chemistry is
branch of chemistry that uses computer simulation to assist in solving chemical problems.
Drug treating AIDS (HIV virus) is
HIV protease inhibitor (block the enzyme in HIV virus)
Ibrutinib is
cancerous B cells drug–> blocking enzyme overexpressed in B cells malignancies
enzyme PCSK9 is
enzyme that normally delays the removal of LDL-C via LDL-R into the liver.
Action of enzyme PCSK9: (in the hepatocyte)
LDL particle taken in by binding to the LDL receptor–> LDL particle is digested(destruction of lysosome in the liver) and broken down inside the cell.
PCSK9 inhibitor effect:
LDL receptors will not be degraded, it will be recycled and re-expressed back onto the surface. (more receptors for more LDL-C for degradation)
breast cancer specific targets:
Blocking HER2 protein.
Infliximab is what type of MAb:
chimeric IgG1 MAb drugs binding to TNFa (tumor necrosis factor)
Colorectal carcinoma receptors:
EGFR (epidermal growth factor receptor)
VEGFR1 (vascular endothelial growth factor receptor 1)
During pre-clinical evaluation, we can do:
initial pharmacokinetics studies (on animal)
