Probes
A component of the NIH Center for Translational Therapeutics (NCTT) is our role within the NIH Molecular Libraries Initiative (MLI). The MLI is mandated to bring advanced technologies and expertise to researchers who lack the means to perform high-throughput screens and follow-up medicinal chemistry efforts, in order to identify and optimize small molecule probes of novel, unexplored cellular targets. These reagents offer the research community much needed proof-of-concept pharmacological tools that may serve as starting points for therapeutic development into clinical agents. Results from these projects are disseminated to the scientific community through the publicly accessible PubChem database and via peer-reviewed publications. This highly collaborative program merges academic researchers' wide-ranging expertise within the study of new biochemical targets and pathways with the translational infrastructure of the NCTT. To date, NCTT scientists, in collaboration with hundreds of extramural scientists, have developed over 60 probes that are freely accessible to the scientific community. A number of NCTT probes are exemplified by the Probe Reports shown below:
Project: Activators for Human Pyruvate Kinase M2 (hPK) as Leads in Cancer Therapeutics
Probe Report: Identification of activators for the M2 isoform of human pyruvate kinase Version 3
Assay Provider: Dr. Matthew G. Vander Heiden, Koch Institute at MIT and Dana Farber Cancer Institute
Project: Inhibitors of Caspase 1 for the treatment of numerous autoimmune and inflammatory diseases
Probe Report: A small molecule inhibitor of Caspase 1
Assay Provider: Dr. Theodore R. Holman, University of California, Santa Cruz
Project: Inhibitors of 12-human lipoxygenase (12-hLO) for the treatment of diabetes and clotting
Probe Report: Selective Small Molecule Inhibitors of 12-human lipoxygenase (12-hLO)
Assay Provider: Dr. Theodore R. Holman, University of California, Santa Cruz
Project: Inhibitors of Cruzain as Therapeutic Leads for Chagas Disease
Probe Report: Inhibitors of Cruzain as Therapeutic Leads for Chagas Disease
Assay Provider: Dr. Brian Shoichet, University of California, San Francisco
Project: Inhibitors of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (HPGD) for the study of prostaglandin's role in inflammation
Probe Report: Potent and selective inhibitors of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (HPGD)
Assay Provider: Dr. Udo Oppermann, Structural Genomics Consortium, University of Oxford
Project: Inhibitors of Cdc2-like kinase 4 (Clk4) to elucidate the mechanism and controlling gene splicing
Probe Report: An inhibitor of the Cdc2-like kinase 4 (Clk4)
Assay Provider: Dr. Tom Misteli, National Cancer Institute, National Institutes of Health
Project: Agonists of the thyroid stimulating hormone receptor for the treatment of Graves' disease
Probe Report: Identification of Potent and Selective Thyroid Stimulating Hormone Receptor Agonists
Assay Provider: Dr. Marvin Gershengorn, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Project: Identification of Inhibitors of the N370S Mutant Form of Glucocerebrosidase as a Potential Therapy for Gaucher Disease
Probe Reports:
- Identification of Modulators of the N370S Mutant Form of Glucocerebrosidase as a Potential Therapy for Gaucher Disease-1
- Identification of Modulators of the N370S Mutant Form of Glucocerebrosidase as a Potential Therapy for Gaucher Disease-2
Assay Provider: Dr. Ellen Sidransky, National Human Genome Research Institute, National Institutes of Health
Project: Identification of SMN modulators for potential SMA disease therapeutics
Probe Report: Discovery, SAR and Biological Evaluation of Aryl-thiazol-piperidines as SMN Modulators
Assay Provider: Dr. Elliot Androphy, University of Massachusetts Medical School
Project: Inhibitors of Platelet Integrin αIIbβ3
Probe Report: Inhibitors of Platelet Integrin αIIbβ3
Assay Provider: Dr. Barry Coller, Rockefeller University
Project: Identification of Novel Small Molecule Antagonists of the Neuropeptide-S Receptor
Probe Report: Identification of Novel Small Molecule Antagonists of the Neuropeptide-S Receptor
Assay Provider: Dr. Markus Heilig, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health
Project: Inhibitors of Schistosoma Mansoni Redox Cascade
Probe Report: Inhibitors of Schistosoma Mansoni Redox Cascade
Assay Provider: Dr. David Williams, Rush University Medical Center
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Last Updated: August 19, 2011
