Kenneth Pearce, Jr, Ph.D.
Professor, Chemical Biology and Medicinal Chemistry
Director, Center for Integrative Chemical Biology and Drug Discovery
Director, Lead Discovery and Characterization
PHONE(919) 843-8461
khpearce@unc.edu
ADDRESS
3012 Marsico Hall, 125 Mason Farm Road, CB# 7363, Chapel Hill, NC, 27599
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Ken Pearce, Ph D is the director of the Center for Integrative Chemical Biology and Drug Discovery. Pearce’s primary expertise and interests are fundamentals of protein methods, biochemical and cell assay development, medium- and high-throughput screening, hit validation and mode-of-action, biophysical methods for characterizing protein-protein and small molecule-protein interactions, and structure-activity relationships for early drug discovery. He joined the center as director of lead discovery and characterization in mid-2015 after spending over 18 years at GlaxoSmithKline and legacy companies in the Molecular Discovery Research organization.
Pearce started his career in anti-infectives discovery at SmithKline Beecham where he studied the cell division protein ftsZ and other essential cell division proteins as potential anti-microbial drug targets. At GlaxoSmithKline, Pearce worked on and led numerous drug discovery efforts for a variety of target classes and therapeutic areas. The majority of his research at GlaxoSmithKline was focused on signal transduction and small molecule modulation of nuclear receptors. He led and contributed to numerous efforts in this area that led to novel drug candidates for cancer and menopausal symptoms (estrogen receptor alpha), metabolic disorders (estrogen-related receptor alpha) and asthma and inflammatory diseases (glucocorticoid receptor). One particular discovery effort included a comprehensive analysis of multiple nuclear receptors and modulating ligands by conformation-sensing peptides utilizing phage display and multiplexed fluorescent bead analysis. For the glucocorticoid receptor, which is one of the most studied and highly validated drug targets for immune-related diseases, these efforts led to the first reported crystal structure and characterization of several marketed products (fluticasone propionate and fluticasone furoate), as well as support for a nonsteroidal agonist program.
For the past several years, Pearce has initiated and led a multi-target program for drug discovery for the proprotein convertase family of enzymes.
Research
Currently within the CICBDD Lead Discovery and Characterization Team, we develop comprehensive early drug discovery programs using a variety of methods including protein expression and purification, biochemical and cell assays, and screening in partnership with numerous collaborators at UNC. We have the ability to conduct compound screening using a library of over 200,000 drug-like small molecules assembled within the center. Our expertise is also in hit validation and triage methods, including use of biophysical methods. Following successful hit discovery and validation, we work with collaborators and chemists within the center to produce structure-activity data and additional mode-of-action studies. Our ultimate goals are to: 1) produce high quality chemical probes for exploring biology of drug targets, and 2) discover drug candidate molecules for treatment of unmet medical needs.
The majority of our activities and interests are exploring targets within the epigenetic and chromatin modification network and prosecuting novel targets, including signal transduction proteins, enzymes and protein-protein interactions, for discovery of new potential cancer treatments.
Publications
- Repurposing the Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine and Pyronaridine: In vitro Activity Against SARS-CoV-2 and Potential Mechanisms.
- A High-Throughput Assay to Identify Allosteric Inhibitors of the PLC-γ Isozymes Operating at Membranes.
- Discovery and Characterization of Peptide Inhibitors for Calcium and Integrin Binding Protein 1.
- Design and Construction of a Focused DNA-Encoded Library for Multivalent Chromatin Reader Proteins.
- Degradation of Polycomb Repressive Complex 2 with an EED-Targeted Bivalent Chemical Degrader.
- Small molecule screening identifies inhibitors of the Epstein-Barr virus deubiquitinating enzyme, BPLF1.
- Targeting Regorafenib-Induced Toxicity through Inhibition of Gut Microbial β-Glucuronidases.
- Discovery and Characterization of a Cellular Potent Positive Allosteric Modulator of the Polycomb Repressive Complex 1 Chromodomain, CBX7.
- Application of a MYC degradation screen identifies sensitivity to CDK9 inhibitors in KRAS-mutant pancreatic cancer.
- A General TR-FRET Assay Platform for High-Throughput Screening and Characterizing Inhibitors of Methyl-Lysine Reader Proteins.
1989: B.S. Chemistry, University of Richmond
1993: Ph.D. Chemistry (Biological Division), University of North Carolina at Chapel Hill
1996: Postdoctoral, Protein Engineering, Genentech, Inc.
1996 – 1998: Scientist, Department of Anti-Infectives, SmithKline Beecham
1998 – 2001: Scientist, Discovery Research, GlaxoWellcome
2001 – 2015: Scientist and Group Leader, Molecular Discovery Research, GlaxoSmithKline
2015 – 2021: Research Professor and Director, Lead Discovery and Characterization, Center for Integrative Chemical Biology and Drug Discovery lab, UNC Eshelman School of Pharmacy
2021 – Present: Research Professor; Director of the Center for Integrative Chemical Biology and Drug Discovery and Director, Lead Discovery and Characterization lab, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy