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Möbitz H, Machauer R, Holzer P, et al. Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach. ACS Med Chem Lett. 2017;8(3):338-343doi: 10.1021/acsmedchemlett.6b00519.
Möbitz, H., Machauer, R., Holzer, P., Vaupel, A., Stauffer, F., Ragot, C., Caravatti, G., Scheufler, C., Fernandez, C., Hommel, U., Tiedt, R., Beyer, K. S., Chen, C., Zhu, H., & Gaul, C. (2017). Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach. ACS medicinal chemistry letters, 8(3), 338-343. https://doi.org/10.1021/acsmedchemlett.6b00519
Möbitz, Henrik, et al. "Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach." ACS medicinal chemistry letters vol. 8,3 (2017): 338-343. doi: https://doi.org/10.1021/acsmedchemlett.6b00519
Möbitz H, Machauer R, Holzer P, Vaupel A, Stauffer F, Ragot C, Caravatti G, Scheufler C, Fernandez C, Hommel U, Tiedt R, Beyer KS, Chen C, Zhu H, Gaul C. Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach. ACS Med Chem Lett. 2017 Feb 14;8(3):338-343. doi: 10.1021/acsmedchemlett.6b00519. eCollection 2017 Mar 09. PMID: 28337327; PMCID: PMC5346981.
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ACS Med Chem Lett. 2017 Feb 14;8(3):338-343. doi: 10.1021/acsmedchemlett.6b00519. eCollection 2017 Mar 09.

Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach.

ACS medicinal chemistry letters

Henrik Möbitz, Rainer Machauer, Philipp Holzer, Andrea Vaupel, Frédéric Stauffer, Christian Ragot, Giorgio Caravatti, Clemens Scheufler, Cesar Fernandez, Ulrich Hommel, Ralph Tiedt, Kim S Beyer, Chao Chen, Hugh Zhu, Christoph Gaul

Affiliations

  1. Novartis Institutes for Biomedical Research , 4002 Basel, Switzerland.
  2. Novartis Institutes for Biomedical Research , Shanghai 201203, China.

PMID: 28337327 PMCID: PMC5346981 DOI: 10.1021/acsmedchemlett.6b00519

Abstract

Misdirected catalytic activity of histone methyltransferase Dot1L is believed to be causative for a subset of highly aggressive acute leukemias. Targeting the catalytic domain of Dot1L represents a potential therapeutic approach for these leukemias. In the context of a comprehensive Dot1L hit finding strategy, a knowledge-based virtual screen of the Dot1L SAM binding pocket led to the discovery of

Keywords: Dot1L; fragment linking; inhibitor; mixed lineage leukemia; protein lysine methyltransferase

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