MODULATORS OF G PROTEIN-COUPLED FORMYL PEPTIDE RECEPTOR-LIKE 2 AND THEIR THERAPEUTIC USE AGAINST CELL DEATH-RELATED DISORDERS

摘要

The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In certain embodiments, the GPCR is human. In certain embodiments, the GPCR is expressed endogenously by neuronal cells or muscle cells. In certain embodiments, the GPCR is neuroprotective or myoprotective. In certain embodiments, the GPCR is a Humanin receptor. The present invention also relates to methods of using a modulator of said GPCR. A preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of neurodegenerative diseases in general, including Alzheimer's disease, Parkinson's disease, prion-associated disease, stroke and motor-neuron disease in particular, peripheral neuropathy, cerebral amyloid beta-protein angiopathy, and ischemic heart disease, including myocardial infarction and congestive heart failure. Podocarpa-8, 11, 13-trien-16-amide derivatives carrying at least a substituent on the aromatic ring are the identified modulators.