Redox active or thiol reactive? : optimization of rapid screens to identify less evident nuisance compounds

Proj, Matic (avtor), Knez, Damijan (avtor), Sosič, Izidor (avtor), Gobec, Stanislav (avtor)

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.

• Jezik: Angleški jezik
• Ključne besede: redox, covalent, screening, hits, PAINS, assays
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.02 - Pregledni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: Str. 1733-1742
• Številčenje: Vol. 27, no. 6
• PID: 20.500.12556/RUL-139090
• UDK: 615.4:54
• ISSN pri članku: 1359-6446
• DOI: 10.1016/j.drudis.2022.03.008
• COBISS.SI-ID: 100881923
• Datum objave v RUL: 30.08.2022

Gradivo je del revije

• Naslov: Drug discovery today
• Skrajšan naslov: Drug discov. today
• Založnik: Elsevier
• ISSN: 1359-6446
• COBISS.SI-ID: 1216021

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: redoks, kovalentni presejalni pregled, testi, farmacevtska kemija, zdravila

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin