2013-10-04 17:45:36 - OTAVA focused library of 5-HT1B antagonists (1,836 compounds in total) has been designed using receptor-based virtual screening of pre-filtered compound collection docked into orthosteric and extended pockets of the 5-HT1B ligand binding site.
5-HT1B serotonin receptors are involved in regulation of several physiological functions, behavior and psychiatric diseases including locomotor activity, vascular smooth muscle constriction, aggressive behavior, migraine, depression and anxiety states. Inactivation of 5-HT1B receptors might affect attention and emotion and have positive effects on learning and memory processes. However, clinical application of 5-HT1B receptor inhibitors can cause unexpected side effects arising from interactions with other 5-HT receptor subtypes. The lack of specific 5-HT1B antagonists led OTAVA to design focused library containing compounds specifically targeted towards 5-HT1B receptor in such a way to minimize cross-reactivity with 5-HT2B receptor.
The 5-HT1B subtype-targeted antagonists have been selected with inspection of active site critical structural determinants for ligand recognition, validation of reference set of
26 known 5-HT antagonists and exclusion of predicted 5-HT2B binders from the final set of compounds by similarity analysis and docking score cut-off filtering. In order to increase the potential for blood-brain barrier penetration, the library falls into the following physicochemical property ranges: MolWeight < 450, number of H donors ≤ 3, number of H acceptors ≤ 9, CLogP 2-5, LogD 2-5 and PSA < 90.
We hope that OTAVA’s focused library of 5-HT1B antagonists will help drug discovery scientists to develop treatments based on the inhibition of this subtype of serotonin receptors.