Lecture 3

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Lecture 3
2013-01-22 23:00:55
CHE 130A

HTS, rational design, Viagra
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  1. High throughput screening (HTS)
    ~100,000 compounds screened to get lead compounds
  2. Random Screen
    Large library of compounds
  3. Focused Screen
    Restrict to a smaller # of compounds that are structurally related
  4. Rational design
    a) Natural product is known to be active --> make changes in the compound to generate lead

    b) If target is known + have a structure that is known ~ predict compounds that would bind computationally.
  5. Things to consider about drug screening
    1) A metabolite may be the actual drug.

    2) A second activity may be identified in clinical trials (good or bad)

    3) A positive effect is discovered which can be a Lead for a new therapeutic.
  6. UK921480 --> Viagra
    UK921480 designed for hypertension and blocks activity of cGMP phosphodiesterase.

    It inhibited that in the penis which led to more cGMP (high blood flow) so gives erections.
  7. Lead Modification
    • 1. Identify the pharmacophore.
    • 2. Identify the auxophore which could be "extra" or stabilizing/interfering with the pharmacophore.
  8. Determining the pharmacophore
    By making derivatives + testing toward target.