Recent studies have shown that the overexpression of serine/threonine protein phosphatase 5 (PP5) is associated with invasive ductal carcinoma of the breast, cancer cell proliferation, and resistance to apoptosis. However, scientists currently lack the molecular equipment with which to further characterize the biological role of PP5 in tumorigenesis. For the purpose of investigating this role, small molecule inhibitors of the catalytic subunit of PP5 (PP5C) may be useful as chemical probes. LB100 is a small molecule inhibitor that is structurally similar to cantharidin, a natural product of the Mexican bean beetle. LB100 is a potent inhibitor of PP2A that is currently in phase I clinical trials, but our group shows that LB100 is also a potent inhibitor of PP5C at nanomolar concentrations. Based on the structure of LB100 and its similarity to cantharidin, our group has devised a synthetic scheme to create a library of useful chemical probes. Several analogs were synthesized using this scheme, and their activity against PP5C was evaluated by means of a homogenous fluorescence intensity-based assay.

Synthesis of chemical probes for serine/threonine protein phosphatase 5C based on a natural product template

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.