An article published this year in “NUCLEIC ACIDS RESEARCH” using our Annexin
V-FITC and 7-aminoactinomycin D (7-AAD), by our customers from Hospital
Universitario La Paz-IdiPAZ, and CIBER
de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain, in
the study of New inhibitor targeting human transcription factor HSF1: effects
on the heat shock response and tumor cell survival. Congrats and Thanks.
Summary:
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 transcriptional activity of human HSF1, interfering with the assembly of ATF1-containing transcription complexes. IHSF115 was employed to probe the human heat shock response at the transcriptome level. In contrast to earlier studies of differential regulation in HSF1-naıve and -depleted cells, our results suggest that a large majority of heat-induced genes is positively regulated by HSF1. That IHSF115 effectively countermanded repression in a significant fraction of heat-repressed genes suggests that repression of these genes is mediated by transcriptionally active
HSF1. IHSF115 is
cytotoxic for a variety of human cancer cell lines, multiple myeloma lines consistently exhibiting high sensitivity.
Reference:
Product link:
FITC Annexin V Apoptosis Detection Kit with 7-AAD: http://www.immunostep.com/apoptosis-tools/3741-anxvkf-100t.html
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