Tuomo Kalliokoski, Henna Kettunen, Esa Kumpulainen, Emilia Kettunen, Gabriel Thieulin-Pardo, Lars Neumann, Maren Thomsen, Ralf Paul, Alina Malyutina, Maria Georgiadou
Bioorganic & medicinal chemistry letters 2023 Oct 01Methionine adenosyltransferase 2A (MAT2A) has been indicated as a drug target for oncology indications. Clinical trials with MAT2A inhibitors are currently on-going. Here, a structure-based virtual screening campaign was performed on the commercially available chemical space which yielded two novel MAT2A-inhibitor chemical series. The binding modes of the compounds were confirmed with X-ray crystallography. Both series have acceptable physicochemical properties and show nanomolar activity in the biochemical MAT2A inhibition assay and single-digit micromolar activity in the proliferation assay (MTAP -/- cell line). The identified compounds and the relating structural data could be helpful in related drug discovery projects. Copyright © 2023 Elsevier Ltd. All rights reserved.
Tuomo Kalliokoski, Henna Kettunen, Esa Kumpulainen, Emilia Kettunen, Gabriel Thieulin-Pardo, Lars Neumann, Maren Thomsen, Ralf Paul, Alina Malyutina, Maria Georgiadou. Discovery of novel methionine adenosyltransferase 2A (MAT2A) allosteric inhibitors by structure-based virtual screening. Bioorganic & medicinal chemistry letters. 2023 Oct 01;94:129450
PMID: 37591318
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