From owner-chemistry- at -ccl.net Thu Mar 3 11:52:01 2016 From: "Pavel Polishchuk pavel_polishchuk|*|ukr.net" To: CCL Subject: CCL: Pharmacophore: a question of semantics Message-Id: <-52096-160303103317-1854-WPWx1/ehrTD+y4VPnCLilQ[A]server.ccl.net> X-Original-From: Pavel Polishchuk Content-Transfer-Encoding: 8bit Content-Type: text/plain; charset=windows-1251 Date: Thu, 3 Mar 2016 16:33:03 +0100 MIME-Version: 1.0 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.