Screening of big pharma’s library against various in-house biological targets

Knez, Damijan (author), Gobec, Stanislav (author), Hrast, Martina (author)

Open innovation initiatives provide opportunities for collaboration and sharing of knowledge and experience between industry, academia, and government institutions. Through open innovation, Merck is offering a Mini Library of 80 carefully selected compounds from previous research and development projects to a broader scientific community for testing in academic drug discovery projects. These compounds are predominantly drug-like and cover a broad range of molecular targets. They could potentially interact with other enzymes, receptors, transporters, and ion channels of interest. The Mini Library was tested on seven in-house enzymes (bacterial MurA, MurC ligase, and DdlB enzyme, human MAO-A/B, human BChE, and murine AChE), and several hits were identified. A follow-up series of structural analogues provided by Merck gave a more detailed insight into the accessibility and the quality of the hit compounds. For example, sartan derivatives were moderate inhibitors of MurC, whereas bisarylureas were potent, selective, nanomolar inhibitors of hMAO-B. Importantly, 3-n-butyl-substituted indoles were identified as low nanomolar selective inhibitors of hBChE. All in all, the hit derivatives provide new starting points for the further exploration of the chemical space of high-quality enzyme inhibitors.

• Language: English
• Keywords: Merck Mini Library, screening, MurA, MurC, human MAO-A/B, human BChE, murine AchE
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Publication date: 13.08.2022
• Year: 2022
• Number of pages: 12 str.
• Numbering: Vol. 27, iss. 14, art. 4484
• PID: 20.500.12556/RUL-138679
• UDC: 615.4:54
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules27144484
• COBISS.SI-ID: 117586947
• Publication date in RUL: 09.08.2022

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 09.08.2022

Secondary language

• Language: Slovenian
• Keywords: Merckova mini knjižnica, pregledovanje, humani MAO-A/B, humani BChE, mišji AchE