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Article

Discovery of Novel eEF2K Inhibitors Using HTS Fingerprint Generated from Predicted Profiling of Compound-Protein Interactions

1
Institute for Theoretical Medicine, Inc., 26-1, Muraoka-Higashi 2-chome, Fujisawa 251-0012, Japan
2
INTAGE Healthcare, Inc., 79, Kankoboko-cho, Shimogyo-ku, Kyoto 600-8009, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: William Cho
Medicines 2021, 8(5), 23; https://doi.org/10.3390/medicines8050023
Received: 26 March 2021 / Revised: 24 April 2021 / Accepted: 18 May 2021 / Published: 20 May 2021
(This article belongs to the Special Issue Feature Papers in Cancer Biology and Anticancer Therapeutics)
Background: Eukaryotic elongation factor 2 kinase (eEF2K) regulates the elongation stage of protein synthesis by phosphorylating eEF2, a process related to various diseases including cancer and cardiovascular and neurodegenerative diseases. In this study, we describe the identification of novel eEF2K inhibitors using high-throughput screening fingerprints (HTSFP) generated from predicted profiling of compound-protein interactions (CPIs). Methods: We utilized computationally generated HTSFPs referred to as chemical genomics-based fingerprint (CGBFP). Generally, HTSFPs are generated from multiple biochemical or cell-based assay data. On the other hand, CGBFPs are generated from computational prediction of CPIs using the Chemical Genomics-Based Virtual Screening (CGBVS) method. Therefore, CGBFPs do not have missing information mainly caused by the absence of assay data. Results: Chemogenomics-Based Similarity Profiling (CGBSP) of the screening library (2.6 million compounds) yielded 27 compounds which were evaluated for in vitro eEF2K inhibitory activity. Three compounds with interesting results were identified. Compounds 2 (IC50 = 11.05 μM) and 4 (IC50 = 43.54 μM) are thieno[2,3-b]pyridine derivatives that have the same scaffolds with a known eEF2K inhibitor, while compound 13 (IC50 = 70.13 μM) was a new thiophene-2-amine-type eEF2K inhibitor. Conclusions: CGBSP supplied an efficient strategy in the identification of novel eEF2K inhibitors and provided useful scaffolds for optimization. View Full-Text
Keywords: eEF2K—Eukaryotic elongation factor-2 kinase; CGBFP—chemical genomics-based fingerprint; CGBVS—Chemical Genomics-Based Virtual Screening; CGBSP—Chemical Genomics-Based Similarity Profiling eEF2K—Eukaryotic elongation factor-2 kinase; CGBFP—chemical genomics-based fingerprint; CGBVS—Chemical Genomics-Based Virtual Screening; CGBSP—Chemical Genomics-Based Similarity Profiling
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MDPI and ACS Style

Yoshimori, A.; Kawasaki, E.; Murakami, R.; Kanai, C. Discovery of Novel eEF2K Inhibitors Using HTS Fingerprint Generated from Predicted Profiling of Compound-Protein Interactions. Medicines 2021, 8, 23. https://doi.org/10.3390/medicines8050023

AMA Style

Yoshimori A, Kawasaki E, Murakami R, Kanai C. Discovery of Novel eEF2K Inhibitors Using HTS Fingerprint Generated from Predicted Profiling of Compound-Protein Interactions. Medicines. 2021; 8(5):23. https://doi.org/10.3390/medicines8050023

Chicago/Turabian Style

Yoshimori, Atsushi, Enzo Kawasaki, Ryuta Murakami, and Chisato Kanai. 2021. "Discovery of Novel eEF2K Inhibitors Using HTS Fingerprint Generated from Predicted Profiling of Compound-Protein Interactions" Medicines 8, no. 5: 23. https://doi.org/10.3390/medicines8050023

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