Functional antagonists of the Apelin (APJ) receptor
- PMID: 23658961
- Bookshelf ID: NBK133430
Functional antagonists of the Apelin (APJ) receptor
Excerpt
The recently discovered apelin receptor (APJ, AGTRL-1, APLNR) system has emerged as a critical mediator of cardiovascular homeostasis and is involved in the pathogenesis of hypertension, heart failure, atherosclerosis, and other cardiovascular diseases. We disclose the first discovery and characterization of a potent (1.7 – 2.2 μM), kojic acid based small molecule APJ functional antagonist in cell-based assays that is >37 fold selective over the closely related angiotensin II type 1 (AT1) receptor, derived from an high throughput screening (HTS) of the ~330,600 compound MLSMR collection. This antagonist showed no significant binding activity against 29 other GPCRs, except to the κ-opioid receptor (<50%I at 10 μM). The synthetic methodology, development of structure-activity relationship (SAR), and initial in vitro pharmacologic characterization are also presented. This probe molecule provides a useful tool compound for investigators interested in understanding apelin receptor pharmacology and function.
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References
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