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PHRD5915 Drug Design Lecture 9 - Drug-Receptor Binding II

  1. polyol pathway
    glucose --(AR)--> sorbitol --(SDH)--> fructose
  2. involvement of polyol pathway in diabetic complications
    sorbitol accumulation leads to crystallization & opafication of eye lens
  3. first & rate-limiting step of the polyol pathway
    glucose --(AR)--> sorbitol
  4. cofactors involved in polyol pathway
    • NADPH
    • NAD+
  5. major cause of various complications of secondary diabetes
    • 1) accumulation of sorbitol
    • 2) oxidative stress due to changes in ratio of NADPH/NADP+ & reduced NADH/NAD+
  6. AR proton donor (H-bond acceptor) residue
    Tyr48
  7. Image Upload 2
    spirohydantoin ring
  8. sulfonylurea:
    1) molecular target
    2) disease/symptom
    • 1) K+ channels in pancreatic Image Upload 4-cells 
    • 2) T2DM
  9. sulfonylurea MOA
    bind & close K+ channels stimulating secretion of insulin
  10. Metformin (biguanide):
    1) molecular target
    2) disease/symptom
    • 1) AMP-activated PK
    • 2) T2DM
  11. Metformin (biguanide) MOA
    AMPK agonist that blocks gluconeogenesis
  12. insulin:
    1) molecular target
    2) disease/symptom
    • 1) insulin-R's
    • 2) type I diabetes & severe T2DM
  13. insulin MOA
    facilitate glucose transport into cells
  14. thiazolinediones:
    1) molecular target
    2) disease/symptom
    • 1) PPARImage Upload 6 nuclear R's
    • 2) T2DM
  15. thiazolinedione MOA
    agonist of PPARImage Upload 8 decreasing insulin resistance
  16. aldose reductase inhibitors (ARI's):
    1) molecular target
    2) disease/symptom
    • 1) aldose reductase (AKR1B1)
    • 2) no approved indications
  17. ARI MOA
    blocks conversion of glucose to sorbitol under hyperglycemic conditions (implicated in diabetic complications)
Author
daynuhmay
ID
274095
Card Set
PHRD5915 Drug Design Lecture 9 - Drug-Receptor Binding II
Description
Drug-Receptor Binding
Updated

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