Jacobson, Kenneth (NIDDK)
Research quantities of compounds have been synthesized and tested for receptor selectivity.
This invention claims species-independent agonists of A3AR, specifically (N)-methanocarba adenine nucleosides and pharmaceutical compositions comprising such nucleosides. The A3 adenosine receptor (A3AR) subtype has been linked with helping protect the heart from ischemia, controlling inflammation, and regulating cell proliferation. Agonists of the human A3AR subtype have been developed that are also selective for the mouse A3AR while retaining selectivity for the human receptor. This solves a problem for clinical development because animal model testing is important for pre-clinical validation of drug function. Novel agonists have been made that exhibit as much as 6000x selectivity for A3 versus A1 in humans while retaining at least 400x selectivity for A3 versus A1 in mice. In addition, the molecules of the invention exhibit very low nanomolar affinity. This innovation will not only facilitate moving A3 agonists into the clinical phase of drug development by being more amenable to animal studies, but also provide much greater selectivity in humans, and thereby potentially fewer side effects than drugs currently undergoing clinical trials.
- cardiac arrhythmias or ischemia