Monoclonal antibodies as surrogate receptors in a high throughput screen for compounds that enhance insulin sensitivity
| Autor: | Frank C. Tinsley, Scott W. Sage, Schmiegel Klaus K, Lora Louise Fitch, Samuel J. Dominianni, Stuart W. Bright, J. Richard Sportsman, Marcia L. Kellam, Terence T. Yen, Gerald Gold |
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| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.drug_class Receptors Cytoplasmic and Nuclear Peroxisome proliferator-activated receptor Biology Monoclonal antibody General Biochemistry Genetics and Molecular Biology Mice Structure-Activity Relationship Troglitazone medicine Animals Hypoglycemic Agents Insulin Potency Chromans General Pharmacology Toxicology and Pharmaceutics Thiazolidinedione Enhancer Receptor chemistry.chemical_classification Mice Inbred BALB C Antibodies Monoclonal Insulin sensitivity General Medicine Peroxisome Thiazoles chemistry Biochemistry Thiazolidinediones Transcription Factors |
| Zdroj: | Life Sciences. 61:2305-2315 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/s0024-3205(97)00934-x |
| Popis: | Monoclonal antibodies (MoAbs) were made to a known insulin sensitivity enhancer (ISE) compound, CS-045. The MoAbs were characterized with respect to binding other known thiazolidinedione ISE compounds using a CS-045 labeled with b-phycoerythrin in a competitive particle concentration fluorescence immunoassay (PCFIA). By comparing the rank order of IC 50 values for each compound to its respective potency as an ISE, one MoAb (13E3) was selected for further characterization. This MoAb was also used as a surrogate receptor in a high throughput screen to identify novel compounds that compete for binding to CS-045. Some of the hits were found to have efficacy in reducing blood glucose. Subsequently, another group reported that several compounds with the core thiazolidinedione structure of the ISE compounds bound with high affinity to peroxisome proliferator-activating receptors (PPAR). Therefore, we used the MoAb assay to test these and other compounds that are known to bind to PPARy and noted crossreactivity with some of the compounds. |
| Databáze: | OpenAIRE |
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