From Hit to Lead: Structure-Activity Relationships · seed 1 · A4, ink-friendly. The answer key prints on its own page for grown-ups.

From screening hit to lead compound

Science · Chemistry · ages 23-24
Name ______________________   Date ____________
  1. Every strong analogue carries an added side chain. The weak ones lack it. What do you conclude?

    • It weakens every compound
    • It has no role at all
    • The target requires that side chain
  2. To learn what one substituent does, which set do you make?

    • Analogues that differ at that spot alone
    • Analogues that change every spot at once
    • Copies of the hit with no changes
  3. A potency gain that disappears under new assay conditions was never real binding.

    Circle one:   True   False

  4. Analogue A is bigger and slightly stronger. Analogue B is smaller with better efficiency. Which is the better lead?

    • Analogue B, by compact strength
    • Analogue A, by raw potency
    • Neither can be judged at all
  5. A compound looks potent but forms clumps in solution. What do you suspect?

    • Strong binding to the target
    • An aggregation artefact
    • A cleaner assay signal
  6. An analogue changes two spots at once and gains potency. What can you claim?

    • Each spot helped equally
    • Nothing about either spot alone
    • The worse spot carried the gain
  7. Each added atom raises potency, but efficiency keeps falling. What should the team do?

    • Keep adding atoms for more potency
    • Stop adding bulk and seek compact gains
    • Restart screening from zero
  8. All strong analogues share a side chain, but one weak analogue has it too. What do you conclude?

    • The side chain is useless
    • The table must be thrown out
    • It helps but is not the whole story
LightMySky · lightmysky.comW1-mt_p53KgFKAUg-s1

Answer key

For grown-ups. Fold this page away before handing over the rest.

From screening hit to lead compound W1-mt_p53KgFKAUg-s1

  1. The target requires that side chain · The pattern points at the side chain. Keep it while you change the rest.
  2. Analogues that differ at that spot alone · One change means one cause. Mixed changes teach nothing.
  3. True · Real binding survives changed conditions. A vanishing gain was an artefact.
  4. Analogue B, by compact strength · Bulk alone can flatter potency. Efficiency points at the true lead.
  5. An aggregation artefact · Clumps can fake activity. Check for aggregation before you celebrate.
  6. Nothing about either spot alone · Two changes share the credit. Split them into single-change analogues.
  7. Stop adding bulk and seek compact gains · Falling efficiency warns of empty bulk. Compact gains are the way forward.
  8. It helps but is not the whole story · One exception breaks the simple rule. The chain helps, yet more decides potency.
Worksheet · LightMySky