New lead discovery for novel M1 agonists: pharmacophore model based on DISCO computation and virtual screening

Abstract

Abstract:

To discover new lead compounds for M₁ agonists. Ten typical M₁ agonists were superimposed to build a M₁ agonists 3D-pharmacophore model using distance-comparisons (DISCO) method without the previous knowledge of the three-dimensional structure of M₁ receptor. Virtual screening strategy was used to analyze the Available Chemicals Directory-Screening Compounds (ACD-SC) to identify possible new hits. Twenty-two compounds which fit the pharmacophore model well and are not similar with known M₁ agonists were purchased in order to evaluate their M₁ receptor agonist activity. One of them shows M₁receptor agonist activity with EC₅₀ of 4.90 μmol/L and maximum response. Multiple of 10.0 which shows it worthy of further study as a new lead compound for M₁ agonists.

Key words: DISCO, DISCO, M1 agonists, M1 agonists, Pharmacophore model, Pharmacophore model, Virtual screening, Virtual screening, Alzheimer's disease, Alzheimer's disease

CLC Number:

R916.1

Supporting:

Guang-Tao Gao, Yan Niu, Dong Wang, Xiao-Ping Lei^*, Ying-He Hu^**. New lead discovery for novel M1 agonists: pharmacophore model based on DISCO computation and virtual screening[J]. .

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