New inhibitor targeting human transcription factor HSF1: effects on the heat shock response and tumor cell survival.

ABSTRACT: Comparative modeling of the DNA-binding domain of human HSF1 facilitated the prediction of possible binding pockets for small molecules and definition of corresponding pharmacophores. In silico screening of a large library of lead-like compounds identified a set of compounds that satisfied the pharmacophoric criteria, a selection of which compounds was purchased to populate a biased sublibrary. A discriminating cell-based screening assay identified compound 001, which was subjected to systematic analysis of structure-activity relationships, resulting in the development of compound 115 (IHSF115). IHSF115 bound to an isolated HSF1 DNA-binding domain fragment. The compound did not affect heat-induced oligomerization, nuclear localization and specific DNA binding but inhibited the transcriptio

SUBMITTER: Vilaboa N 

PROVIDER: S-EPMC5449623 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature