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# Isothermal titration calorimetry in drug development

## Problem

Isothermal Titration Calorimetry (ITC) is a procedure used in pharmaceutical research to identify lead compounds for therapeutic intervention and to optimize the affinity and selectivity of a drug candidate. Alternatively, ITC can be used to elucidate on enzyme kinetics or to confirm its mechanism of action. Unlike previous assays, ITC is more versatile and has applicability to a gamut of different ligands, i.e. proteins, lipids, DNA, ions, with no limit on molecular weight.
The major features of a typical isothermal titration calorimeter are the reference cell, sample cell, syringe, and adiabatic shield. Enclosed within the shield are the sample cell containing the protein target in buffer and the reference cell containing only the buffer. The syringe for adding titrant contains the compound or binding partner. During the experiment, constant power is supplied to the reference cell heater, while power is supplied to the sample cell feedback heater to bring the two samples back to the same temperature due to the difference induced by binding.
Figure 1. Schematic diagram of an isothermal titration calorimetry instrument