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"Discovering druggable sites on class B GPCRs"
Pharmacology & Chemical Biology Seminar Series
10/29/2020 - 12:00 PM-1:00 PM
"Discovering druggable sites on class B GPCRs
"
Ieva Sutkeviciute, Ph.D.
Research Assistant Professor
Department of Pharmacology & Chemical Biology
University of Pittsburgh
School of Medicine
Despite being highly important targets for treatment of numerous disorders including metabolic, cardiovascular and psychiatric, the peptide hormone-binding class B G protein-coupled receptors (GPCRs) are notoriously difficult to drug with small molecule drug candidates due to their structural features. We set out to challenge this problem by investigating the druggability of parathyroid hormone type 1 receptor (PTH1R), a prototypical class B GPCR that is a key regulator of mineral ion homeostasis and bone turnover. Using a combination of computational approaches, we identified an allosteric druggable site in PTH1R and discovered several small molecule compounds that effectively modulate PTH-induced PTH1R signaling in cells as well as gene expression in mice long bones. We also demonstrate that such computational pipeline might be extendable to other class B GPCRs to discover novel druggable allosteric sites.
Contact
Melanie McClain
412/383-7757