ANN ARBOR—The University of Michigan Center for the Discovery of New Medicines has awarded eight grants, totaling $205,000, to projects investigating new treatments for cancer, infectious disease and heart failure.

The support allows U-M researchers to move potential early-stage drug discovery to the next phase of development.

Awards of up to $50,000 support research in U-M drug discovery core laboratories including high-throughput screening, pharmacokinetics and medicinal chemistry. As the pharmaceutical industry decreases investment in early drug discovery research, more academic groups have started to identify compounds that could become drugs and to test and refine those compounds.

The CDNM pilot grants provide a jumpstart to these nontraditional projects to speed their progress toward commercialization and, ultimately, clinical use.

“We’re very impressed with the breadth and creativity of the submissions in this round,” said Alan Saltiel, director of the Life Sciences Institute. “It’s great to see so much growing interest in drug discovery at U-M.”

Founded in 2012, the CDNM brings together U-M experts in all areas of the drug discovery enterprise—including medicinal chemists, structural biologists, pharmacologists and pharmaceutics and drug metabolism researchers—to support early-stage, innovative projects across the university.

As a virtual center, the CDNM provides financial support and mentorship to researchers with promising potential therapeutics in order to leverage existing investments in informatics, robotics and high-throughput screening and to promote new opportunities in drug discovery and development.

The CDNM is supported by the Life Sciences Institute, Office of the Provost, Comprehensive Cancer Center, Department of Internal Medicine, College of Pharmacy, Department of Pathology and the Endowment for the Basic Sciences.

Selected projects include:

Ronald Buckanovich, Internal Medicine. “Isozyme-selective ALDH Inhibitors for Sensitizing Ovarian Cancer Stem-like Cells to Chemotherapy.”

Project summary: Work with the Vahlteich Medicine Chemistry Core to optimize lead inhibitors of an enzyme that allows cancer stem-like cells to resist chemotherapy, blocking the growth of tumors in ovarian cancer.

Gregory Dressler, Pathology. “Identifying Novel Small Molecules for Renal Disease.”

Project summary: High-throughput screening in the Center for Chemical Genomics to identify small molecule inhibitors of Pax2 and define new classes of Pax protein inhibitors that might improve the treatment of urogenital disease and chemotherapy outcomes as well as reduce side effects.

George Garcia, Medicinal Chemistry, College of Pharmacy. “Identification of Novel Inhibitors of MTB RNA Polymerase via HTS.”

Project summary: High-throughput screening in the Center for Chemical Genomics to identify novel inhibitors of RNA polymerase from Mycobacterium tuberculosis, the causative agent of tuberculosis, as potential leads for new drugs for drug-resistant tuberculosis.

Eric Martens, Microbiology and Immunology. “A live cell screen for chemical inhibitors of colitis caused by commensal bacteria.”

Project summary: High-throughput screening in the Center for Chemical Genomics to find chemical inhibitors to block intestinal inflammation in inflammatory bowel disease by inhibiting a physiological behavior that is common to the bacteria that cause the disease, without killing them and destabilizing the microbiota as antibiotics would.

Maria Sandkvist, Microbiology and Immunology. “High throughput screen for the identification of type II secretion inhibitors in Acinetobacter baumannii.”

Project summary: High-throughput screening in the Center for Chemical Genomics to isolate inhibitors of multidrug-resistant strains of Acinetobacter baumannii, an increasingly frequent cause of life-threatening infections in immunocompromised people.

John Tesmer, Life Sciences Institute and Pharmacology. “Synthesis and Characterization of Hybrid Analogs for the Inhibition of G Protein-Coupled Receptor Kinase 2.”

Project summary: Synthesize and test hybrid compounds in the Vahlteich Medicinal Chemistry Core to improve potency, selectivity and bioavailability for small molecule inhibition of specific G protein-coupled receptor kinases involved in heart failure and cardiac hypertrophy.

John Tesmer, Life Sciences Institute and Pharmacology. “High-throughput screening for small molecule inhibitors directed against the PH domain of P-Rex1, an enhancer of metastatic potential.”

Project summary: Develop high-throughput screening in the Center for Chemical Genomics to identify small molecule inhibitors of an enzyme that regulates cell motility and is involved in cancer metastasis.

Matthew Young, Pharmacology. “A non-active site-directed approach to inhibit deubiquitinases for cancer therapy.”

Project summary: Drive the development of optimized cancer therapeutics by determining crystal structures in the Center for Structural Biology of a novel class of enzyme targets whose up-regulation is known to drive certain cancers like leukemia.

The next round of grants will be awarded in early 2015.

Related Link:

• Grant application information: http://cdnm.lsi.umich.edu