Number of the records: 1
Insights into the operational model of agonism of receptor dimers
- 1.
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, ORCIDSource Title Expert Opinion on Drug Discovery. - : Taylor & Francis - ISSN 1746-0441
Roč. 17, č. 11 (2022), s. 1181-1191Number 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 https://doi.org/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