Computational study of drugs targeting nuclear receptors

Maša Kenda (Avtor), Marija Sollner Dolenc (Avtor)

Povzetek

Endocrine-disrupting chemicals have been shown to interfere with the endocrine system function at the level of hormone synthesis, transport, metabolism, binding, action, and elimination. They are associated with several health problems in humans: obesity, diabetes mellitus, infertility, impaired thyroid and neuroendocrine functions, neurodevelopmental problems, and cancer are among them. As drugs are chemicals humans can be frequently exposed to for longer periods of time, special emphasis should be put on their endocrine-disrupting potential. In this study, we conducted a screen of 1046 US-approved and marketed small-molecule drugs (molecular weight between 60 and 600) for estimating their endocrine-disrupting properties. Binding affinity to 12 nuclear receptors was assessed with a molecular-docking program, Endocrine Disruptome. We identified 130 drugs with a high binding affinity to a nuclear receptor that is not their pharmacological target. In a subset of drugs with predicted high binding affinities to a nuclear receptor with Endocrine Disruptome, the positive predictive value was 0.66 when evaluated with in silico results obtained with another molecular docking program, VirtualToxLab, and 0.32 when evaluated with in vitro results from the Tox21 database. Computational screening was proven useful in prioritizing drugs for in vitro testing. We suggest that the novel interactions of drugs with nuclear receptors predicted here are further investigated.

Ključne besede

nuklearni receptorji;molekularno mapiranje;endocrine-disrupting chemicals;drugs;databases;nuclear receptors;molecular docking;multidimensional QSAR;

Podatki

Jezik:	Angleški jezik
Leto izida:	2020
Tipologija:	1.01 - Izvirni znanstveni članek
Organizacija:	UL FFA - Fakulteta za farmacijo
UDK:	615:616.4
COBISS:	4896881
ISSN:	1420-3049
Št. ogledov:	174
Št. prenosov:	61
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarne ključne besede:	Endokrinologija;Zdravila;
Vrsta dela (COBISS):	Članek v reviji
Strani:	str. 1-14
Letnik:	ǂVol. ǂ25
Zvezek:	ǂiss. ǂ7
Čas izdaje:	2020
DOI:	10.3390/molecules25071616
ID:	14010150