Other drug targets Flashcards
Receptor polys don’t usually cause …
Complete loss of activity
B1 and B2 both increase
cAMP
Adrenergic B2 is
Highly polymorphic
What is the most important B2 poly
Amino acid 16 in ligand binding domain
Outside of the cell
G-protein coupling is unaffected
What B2 haplotype is most significant
Haplotype 4 shows reduced response to salbutamol and lower mRNA and protein expression
What is the effect of B2 polys on long lasting agonists
No difference
What is the most common B1 poly and what is its effect
Gly to Arg
Arg form shows enhanced Gs protein interaction and increased adenyl cyclase activation
Most important Vitamin K oxidoreductase C1 (VKORC1) polys
2 non-coding changes in linkage disequilibrium
G to A
C to T
What clinical relevance do the 2 VKORC1 polys have
They are associated with a lower dose requirement of Warfarin due to reduced gene expression
What polys are associated with Warfarin resistance
Polys in the coding region of VKORC1
These affect warfarin binding but not vitamin K epoxide reduction
What reduces warfarin dose even more in VKORC1 poly patients
People heterozygous for CYP2C9 12
What is the most common CFTR poly
Change in F508 (single amino acid deletion)
Protein is not trafficked to membrane
What is the second most common CFTR poly
G551D
Protein is correctly located but does not respond to ligand
What does Ivacaftor do for G551D poly
Takes the place of the ligand
It corrects the dysfunctional gating in G551D
