UHPLC-HRMS study of pharmacokinetics of a novel hybrid cholinesterase inhibitor K1234: A comparison between in silico, in vitro and in vivo data

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F23%3A00558414" target="_blank" >RIV/60162694:G44__/23:00558414 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/22:10449014 RIV/00179906:_____/22:10449014
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0731708522003193?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0731708522003193?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jpba.2022.114898" target="_blank" >10.1016/j.jpba.2022.114898</a>

Result language
angličtina
Original language name
UHPLC-HRMS study of pharmacokinetics of a novel hybrid cholinesterase inhibitor K1234: A comparison between in silico, in vitro and in vivo data
Original language description
Alzheimer's disease (AD) is one of the most common forms of dementia. Current anti-AD therapeutics exploit the cholinergic hypothesis of its pathophysiology; they aim to inhibit cerebral cholinesterases. K1234 is a novel hybrid molecule derived from Huperzine A and 7-MEOTA-huperzine which shows increased potency in acetylcholinesterase inhibition in vitro compared to the compounds themselves. The study focused on description of the pharmacokinetic behaviour of K1234, blood-brain barrier penetration, identification of the main in vitro and in vivo metabolites. K1234 is relatively non-toxic compound, that is rapidly absorbed after i.p. administration reaching C-max within minutes, with extensive distribution into tissues and fast metabolism in mice. The dominant metabolic pathway appears to be glucuronidation of the parent molecule and its phase-I metabolites. The passage of K1234 across the blood-brain-barrier in mice appears to be limited, as it reached only approximately one third of the AUC of plasma.
Czech name
—
Czech description
—

Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10406 - Analytical chemistry

Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Similar results(10)