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Discovery of Pyrrolo[2,3-c]pyridines as Potent and Reversible LSD1 Inhibitors.
Zheng, Canhui; Rej, Rohan Kalyan; Wang, Mi; Huang, Liyue; Fernandez-Salas, Ester; Yang, Chao-Yie; Wang, Shaomeng.
Afiliación
  • Zheng C; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Rej RK; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Wang M; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Huang L; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Fernandez-Salas E; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Yang CY; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, United States.
  • Wang S; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.
ACS Med Chem Lett ; 14(10): 1389-1395, 2023 Oct 12.
Article en En | MEDLINE | ID: mdl-37849536
Lysine specific demethylase 1 (LSD1) acts as an epigenetic eraser by specifically demethylating mono- and histone 3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) residues. LSD1 has been pursued as a promising therapeutic target for the treatment of human cancer, and a number of LSD1 inhibitors have been advanced into clinical development. In the present study, we describe our discovery of pyrrolo[2,3-c]pyridines as a new class of highly potent and reversible LSD1 inhibitors, designed on the basis of a previously reported LSD1 inhibitor GSK-354. Among them, 46 shows an IC50 value of 3.1 nM in inhibition of LSD1 enzymatic activity and inhibits cell growth with IC50 values of 0.6 nM in the MV4;11 acute leukemia cell line and 1.1 nM in the H1417 small-cell lung cancer cell line. Compound 46 (LSD1-UM-109) is a novel, highly potent, and reversible LSD1 inhibitor and serves as a promising lead compound for further optimization.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ACS Med Chem Lett Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ACS Med Chem Lett Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos