Screening for Novel CBS Inhibitors for Cancer Therapy

DESCRIPTION (provided by applicant): Recent studies of the applicants support the role of the endogenous gaseous biological mediator hydrogen sulfide (H2S) in colorectal cancer: selective upregulation of cystathionine-b-synthase (CBS) and the subsequent production of H2S in colonic cancer cells serves as a pro-survival factor by stimulating tumor cell bioenergetics, growth, proliferation, migration and invasion. This work identifies CBS as a novel antitumor target. In order to advance the clinical translation of this concept, we will pursue the following two Aims: Aim #1. To conduct screening a composite library of clinical drugs, drug-like compounds and pharmacologically active molecules (gt5,000 compounds) to identify novel pharmacological inhibitors of CBS, with the aim of drug repurposing for cancer therapy. In Aim #2, Inhibitors identified in the cell-based screen will subsequently enter specificity and selectivty screening, followed by bioenergetics studies and studies of tumor cell proliferation in