Our Science
PolyCore is committed to applying novel science to give patients with Parkinson’s Disease and other CNS disorders better quality of life.

Parkinson’s Disease

Parkinson’s Disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer’s Disease. It affects approximately 1 million people in the United States, with an estimated 60,000 new cases being diagnosed each year. PD is a chronic, progressive movement disorder typically characterized by at least 2 of 4 cardinal features: tremor (mainly at rest), stiffness or rigidity of muscles, bradykinesia (slowness of movement) and gait and balance problems.

PD occurs when nerve cells in a very specific region of the brain called the substantia nigra stop working or die. These nerve cells, or neurons, produce a specific type of neurotransmitter, dopamine, which helps to regulate movement. As dopamine levels in the brain decrease over time, patients experience impaired movement and other symptoms of PD. In addition to the cardinal features of PD, Parkinson’s patients may also experience non-motor symptoms including cognitive impairment, sleep disorders, pain and fatigue.

There is presently no cure for Parkinson’s Disease. The current gold standard for management of PD symptoms is Levodopa (L-dopa), a medication developed in the late 1960s that treats motor symptoms. L-dopa is synthesized in the brain into dopamine and is considered the most important first-line drug for the management of PD. Over time, patients begin to see the beneficial effects (“ON” time) of L-dopa wear off more quickly and they develop motor fluctuations (“OFF” time). Additionally, approximately 50% of patients on L-dopa long-term (longer than four years) experience Levodopa-induced dyskinesia (LID), which is described as involuntary, erratic, writhing movements of the face, arms, legs and/or trunk. Some Parkinson’s patients delay the use of L-dopa because of the concern regarding the development of dyskinesias.




PCT-3012 is a novel D3 receptor agonist that induces G-protein signaling without causing receptor desensitization over time. Traditional dopamine agonists, such as L-dopa, signal through both the G-protein and β-arrestin signaling pathways. It is believed that the β-arrestin pathway is what causes long-term receptor desensitization, resulting in tolerance and hyperactivation of neurons, leading to dyskinesia. PCT-3012 was designed not to recruit or signal through the β-arrestin pathway, thus resulting in an improved compound compared to traditional dopamine agonists.

Mechanism of Action

Dopamine Pathway




In in vivo studies, PCT-3012 has been shown to improve motor symptoms, as well as cognition, without the development of tolerance, dyskinesia or impulsive behavior.  We are currently conducting IND-enabling studies.

Recent Publications

  • Schneider, J. et. Al. A novel dopamine D3R agonist SK609 with norepinephrine transporter inhibition promotes improvement in cognitive task performance in rodent and non-human primate models of Parkinson’s disease. Experimental Neurology. 2021, 335, 113514, https://doi.org/10.1016/j.expneurol.2020.113514.

  • Xu, W. et. al. Biased signaling agonist of dopamine D3 receptor induces receptor internalization independent of β-arrestin recruitment. Pharmacological Research. 2019, 143, 48-57, https://doi.org/10.1016/j.phrs.2019.03.003.

  • Marshall, C., et. al. Selective activation of Dopamine D3 receptors and norepinephrine transporter blockade enhances sustained attention. Neuropharmacology. 2019 148, 178-188, https://doi.org/10.1016/j.neuropharm.2019.01.003.

  • Xu, W. et. al. Functional Characterization of a Novel Series of Biased Signaling Dopamine D3 Receptor Agonists. ACS Chemical Neuroscience. 2017, 8, 3, 486-500, https://doi.org/10.1021/acschemneuro.6b00221.

  • Simms, S. et. al. In vivo characterization of a novel dopamine D3 receptor agonist to treat motor symptoms of Parkinson’s disease. Neuropharmacology. 2016, 100, 106-115, http://dx.doi.org/10.1016/j.neuropharm.2015.04.004.

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