Targeting the transcription factor Myb by small-molecule inhibitors

Small Molecule Inhibitors Targeting the Th17 Cell Transcription Factor RORγt for the Treatment of Autoimmune Diseases

Naïve CD4+ T helper cells can differentiate into Th1, Th2, Th17, T regulatory, Th9 and Th22 cells. Th1 cells are characterized by their production of IFNγ but not IL-4 and IL-5 while Th2 cells are characterized by their expression of IL-4 and IL-5 but not IFNγ. T-bet and GATA3 are the master transcription factors for Th1 and Th2 cells, respectively [1]. Th1 cells mediate cellular immunity again...

Small-Molecule Inhibitors of the SOX18 Transcription Factor.

Pharmacological modulation of transcription factors (TFs) has only met little success over the past four decades. This is mostly due to standard drug discovery approaches centered on blocking protein/DNA binding or interfering with post-translational modifications. Recent advances in the field of TF biology have revealed a central role of protein-protein interaction in their mode of action. In ...

Small molecule transcription factor mimic.

Regulation of gene expression by transcription factors touches many aspects of eukaryotic biology, and its systematic, external control by organic molecules represents a challenge in chemistry. Here we report the design of a completely organic, nonpeptidic compound that mimics a transcription factor. The design takes advantage of the specific DNA-binding affinity of a hairpin polyamide molecule...

Targeting Mycobacterium tuberculosis topoisomerase I by small-molecule inhibitors.

We describe inhibition of Mycobacterium tuberculosis topoisomerase I (MttopoI), an essential mycobacterial enzyme, by two related compounds, imipramine and norclomipramine, of which imipramine is clinically used as an antidepressant. These molecules showed growth inhibition of both Mycobacterium smegmatis and M. tuberculosis cells. The mechanism of action of these two molecules was investigated...

Identification of small molecule inhibitors targeting the Mad2-Cdc20 interaction