Delving into the Latest Updates on DPI-2505 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

δ opioid receptor

Mechanism

δ opioid receptor antagonists(δ-opioid receptor antagonists)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

Glaxo Group Ltd.

Active Organization-

Inactive Organization

Ardent Pharmaceuticals, Inc.

Glaxo Group Ltd.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

Pharmacophores are widely used for rational drug design and include those based on receptor binding sites or on known ligands. To date, ligand-based pharmacophores have typically used one or a small number of conformers of known receptor ligands. However, this method does not take into account the inherent dynamic nature of molecules, which sample a wide range of conformations, any of which could be the bound form. In the present study, molecular dynamics (MD) simulations were used as a means to sample the conformational space of ligands to include all accessible conformers at room temperature in the development of a pharmacophore. On the basis of these conformers, probability distributions of selected distances and angles in a series of delta specific opioid ligands were obtained and correlated with agonist versus antagonist activities. Individually, the distributions did not allow for unique agonist and antagonist pharmacophores to be identified. However, by extending the conformational analysis to two dimensions, a 2D conformationally sampled pharmacophore (CSP) for distinguishing delta receptor agonists and antagonists was developed. Application of this model to the compound DPI2505 suggests that it may have agonist activity. It is anticipated that the CSP method, which does not require alignment of compounds during pharmacophore development, will be a useful tool for obtaining structure-function relationships of ligands particularly in systems where the receptor 3D structure is not known.

100 Deals associated with DPI-2505

Login to view more data