One of the most challenging hurdles in creating safe and effective new medicines for many diseases is finding drugs that are effective without causing off-target cardiac issues, such as cardiac arrythmias. In collaboration with NIDA, scientists at NCATS have developed a series of novel and highly specific dopamine D3 receptor agonists and antagonists that have potential to target and treat Parkinson’s disease, Schizophrenia, Depression, and substance-use disorders including opioid addiction. Important features of these novel chemical compounds are that they exhibit favorable drug-like properties that are likely to make them successful drug candidates, and have reduced human ether-à-gogo-related gene (hERG) liability and effect on potassium channels, which suggests that the compounds may perform better as Dopamine D3 receptor agonists due to a lower propensity to create cardiac arrythmias.
The novel compounds comprise potent and highly selective Dopamine D3 receptor effectors, inclusive of antagonists and agonists, with alleviated hERG liability and desirable pharmacokinetic properties.