Adding Calorimetric Data to Decision Making in Lead Discovery: a Hot Tip

Overview

Journal Nat Rev Drug Discov

Specialty Pharmacology

Date 2009 Dec 5

PMID 19960014

Citations 102

Authors

John E Ladbury

Gerhard Klebe

Ernesto Freire

Affiliations

Soon will be listed here.

Abstract

Recognition of the limitations of high-throughput screening approaches in the discovery of candidate drugs has reawakened interest in structure-based and other rational design methods. Here, we describe how isothermal titration calorimetry can be used to obtain thermodynamic data on the binding of compounds to protein targets. We propose that these data--particularly the change in enthalpy--could provide a valuable, complementary addition to established tools for selecting compounds in lead discovery and for aiding lead optimization.

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