Insights into the operational model of agonism of receptor dimers

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F22%3A00566162" target="_blank" >RIV/67985823:_____/22:00566162 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1080/17460441.2023.2147502" target="_blank" >https://doi.org/10.1080/17460441.2023.2147502</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/17460441.2023.2147502" target="_blank" >10.1080/17460441.2023.2147502</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Insights into the operational model of agonism of receptor dimers

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Insights into the operational model of agonism of receptor dimers

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GJ19-06106Y" target="_blank" >GJ19-06106Y: Analýza signalizačního biasu nově syntetizovaných muskarinových agonistů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Expert Opinion on Drug Discovery

ISSN

1746-0441

e-ISSN

1746-045X

Svazek periodika

17

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

1181-1191

Kód UT WoS článku

000889990400001

EID výsledku v databázi Scopus

2-s2.0-85142285798