TACRINE AND ANTAGONIST OF NMDAR HYBRIDS

HYB-ANTIOX - původní vzorec

Technology Owner
University Hospital Hradec Králové

Inventors
Jan Korábečný
Kamil Kuča
Eugenie Nepovimová
Ondřej Soukup

IPR Status
no patent application

Stage of Development
In-vitro validation

Contact
Lucie Bartošová
lucie.bartosova@fnhk.cz
+420 727 802 314

TACRINE AND ANTAGONIST OF NMDAR HYBRIDS

Background
Alzheimer’s disease (AD) is the most common cause of dementia in people aged 60 years and older, and accounts for approximately 75% of the total dementia cases worldwide. The continuous research in this field has contributed to delineate AD as a multifactorial syndrome with several biological targets involved in its etiology. Thus the curative paradigm of one-compound one-target that has been followed so far has not reached the desired expectations. The research focus moved towards single hybrid molecule targeting two or more mechanisms involved in disease pathophysiology.

Description of the Invention
A combination of the AChE inhibitor and N-methyl-D-aspartate receptor (NMDAR) antagonist (memantine) is now a standard treatment of AD. Therefore there were synthetized hybrid molecules affecting both targets – cholinesterases and NMDAR.  Our hybrids are able to inhibit acetylcholinesterase and butyrylcholinesterase and furthermore inhibit excessive calcium influx induced by chronic overstimulation of the NMDAR in AD patients.

Advantages
Hybrid molecules represent a new and different strategy in the treatment of AD. We suppose that these compounds are able to hit additional targets relevant to AD and thus succeed in overcoming the multifactorial pathogenesis of this disease. These compounds may be beneficial since they would be expected to lessen the hazard of drug-drug interactions and simplify their pharmacodynamic and pharmacokinetic studies.

Competing Technologies
There are currently four approved products for AD: three cholinesterase inhibitors and one NMDA-receptor antagonist, memantine. These currently available therapies for AD provide symptomatic relief and will not cure or prevent the disease from worsening over time. To date there are other 156 drugs undergoing clinical trials in AD, which are at various testing stages. The mechanisms of action of these drugs are varying – e.g. solanezumab, an Aβ – targeting monoclonal antibody, TauRX’sTRx0237, a tau aggregation inhibitor, Lu AE58054 – 5-HT6 antagonist candidate, is a first-in-class symptomatic treatment for AD.

Download in pdf here: technology summary – HYBRID TACRINE NMDA ENG

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