Polypharmacology of Conformationally Locked Methanocarba Nucleosides

Overview

Journal Drug Discov Today

Specialty Pharmacology

Date 2017 Aug 8

PMID 28781163

Citations 12

Authors

Kenneth A Jacobson

Dilip K Tosh

Kiran S Toti

Antonella Ciancetta

Affiliations

Soon will be listed here.

Abstract

A single molecular scaffold can be adapted to interact with diverse targets, either separately or simultaneously. Nucleosides and nucleotides in which ribose is substituted with bicyclo[3.1.0]hexane are an example of a versatile drug-like scaffold for increasing selectivity at their classical targets: kinases, polymerases, adenosine and P2 receptors. Also, by applying structure-based functional group manipulations, rigidified adenosine derivatives can be repurposed to satisfy pharmacophoric requirements of various GPCRs, ion channels, enzymes and transporters, initially detected as off-target activities. Recent examples include 5HT serotonin receptor antagonists and novel dopamine transporter allosteric modulators. This directable target diversity establishes rigid nucleosides as privileged scaffolds.

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