TOX protein, which is an essential chromatin regulator protein that binds to DNA sequence and affect gene expressions epigenetically. Nowadays, there is no known TOX inhibitors in the clinic, whereas the TOX is the key regulator for T-cell exhaustion activity. The TOX inhibitor can be potentially significant for improving the immunotherapy in the clinic.
Though it is known that DNA binding domains of the nuclear proteins can be challenging to bind with small molecules, and in general it is called 'undraggable' domain. Small molecule microarrays (SMMs) is a cutting-edge technique for High through-put screening drug discovery from Koehler lab. This technique helps screen large quantity of small molecules in the library for one specific protein. Once the interaction between the ligand and the protein takes place, we could detect the signal and confirm the inhibition activity.
As the project leader of TOX, I am utilizing the technology to discovery small molecules that inhibit the TOX protein. Inhibition of the TOX inhibitor can be potentially significant for improving the immunotherapy in the clinic.