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Insights into the operational model of agonism of receptor dimers

SYSNO ASEP	0566162
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Insights into the operational model of agonism of receptor dimers
Author(s)	Jakubík, Jan (FGU-C)_{RID, ORCID} Randáková, Alena (FGU-C)_{RID, ORCID}
Source Title	Expert Opinion on Drug Discovery. - : Taylor & Francis - ISSN 1746-0441 Roč. 17, č. 11 (2022), s. 1181-1191
Number of pages	11 s.
Language	eng - English
Country	GB - United Kingdom
Keywords	operational model of agonism ; operational efficacy ; allosteric modulation ; receptor dimers ; GPCRs ; receptor channels
OECD category	Pharmacology and pharmacy
R&D Projects	GJ19-06106Y GA ČR - Czech Science Foundation (CSF)
Method of publishing	Limited access
Institutional support	FGU-C - RVO:67985823
UT WOS	000889990400001
EID SCOPUS	85142285798
DOI	10.1080/17460441.2023.2147502
Annotation	Introduction:Accurate ranking of efficacies and potencies of agonists is essential in the discovery of new selective agonists. For the purpose of system-independent ranking of agonists, the operational model of agonism (OMA) has become a standard. Many receptors function as oligomers which makes functional responses more complex, requiring an extension of the original OMA.Areas covered:Explicit equations of the operational model of agonism of receptor dimers (OMARD) were derived. The OMARD can be applied to any receptor possessing two orthosteric sites. The behavior of OMARD was analyzed to demonstrate its complexity and relation to experimental data. Properties of OMARD and OMA equations were compared to demonstrate their pros and cons.Expert opinion:Extension of OMA by slope factors gives simple equations of functional response that are easy to fit experimental data but results may be inaccurate because of exponentiation of operational efficacy. Also, such equations cannot accommodate bell-shaped curves. Explicit equations of OMARD give accurate results but are complex and tedious to fit experimental data. All operational models use inter-dependent parameters that are a hurdle in the fitting. A good understanding of OMARD behavior helps to overcome such obstacles.
Workplace	Institute of Physiology
Contact	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Year of Publishing	2023
Electronic address	https://doi.org/10.1080/17460441.2023.2147502

Number of the records: 1