CCL: Pharmacophore: a question of semantics



 Sent to CCL by: Pavel Polishchuk [pavel_polishchuk]|[ukr.net]
 Dear Fabrizio,
   You didn't provide information about how your model was obtained
   (what software you used) and how you used it (for screening or
   design purposes). So my answer will be quite general.
   Pharmacophore definition given by IUPAC "A pharmacophore model is an
   ensemble of steric and electronic features that is necessary to ensure
   the optimal supramolecular interactions with a specific biological
   target structure and to trigger (or to block) its biological response"
   does not include any restrictions on the number of compounds and the
   way how this pharmacohphore model was generated.
   (Wermuth, C., et al., Glossary of  terms  used  in  medicinal
   chemistry  (IUPAC  Recommendations 1998). Pure and Applied
   Chemistry, 1998. 70(5): p. 1129-1143.)
   Thus from theoretical point of view I think you are right.
   Practical aspect is that there are a lot of different approaches for
   pharmacophore modeling and not all of them use inactive compounds for
   model generation (e.g. LigandScout). The number of compounds used
   can influence the model quality and thus pharmacophore models should
   be validated on known active and inactive compounds (if they are
   available) or decoys (not preferable). If both your compounds are
   structurally similar and flexible you may obtain dozens of different
   pharmacophore models and without validation you will not be able to
   guess which ones are better.
   Thus, if you validated your pharmacophore then it can be named
   pharmacophore model if not then it could be better to name it
   pharmacohphore hypothesis.
 Kind regards,
 Pavel.