NDLI: Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases

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Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases

Content Provider	MDPI
Author	Logé, Cédric Thiéfaine, Jérôme Dao, Viet Hung Ourliac-Garnier, Isabelle McCarthy, Florence O. Bach, Stéphane Silva, Teresinha Gonçalves da Denevault-Sabourin, Caroline Baratte, Blandine Robert, Thomas Gouilleux, Fabrice Brachet-Botineau, Marie Bazin, Marc-Antoine Marchand, Pascal
Copyright Year	2021
Description	Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[b,d]furan derivatives derived from cercosporamide. Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar $IC_{50}$ value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure–activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity.
Starting Page	6572
e-ISSN	14203049
DOI	10.3390/molecules26216572
Journal	Molecules
Issue Number	21
Volume Number	26
Language	English
Publisher	MDPI
Publisher Date	2021-10-30
Access Restriction	Open
Subject Keyword	Molecules Oncology Cercosporamide Dibenzo[b,d]furan Pim Kinases Clk1 Kinase Kinase Inhibitors Anticancer Agents
Content Type	Text
Resource Type	Article

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