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PCH-2/TRIP13 is stimulated by the combination of C-MAD2 and p31(comet) (scheme 1); mutation of either binding surface of p31(comet) (schemes 2 and 3) eliminates stimulation, as does replacement of C-MAD2 with O-MAD2 (scheme 4).
For 5-HT7R ligandsubstitutioniof of phenyl or 2-thiophene increases activity, as does replacement of the amide linker, especially with sulfonamide.[ 18] Here, some restrictions were applied to investigate the replacement of groups, with the knowledge that different targets might have different activity thresholds.
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