1. Academic Validation
  2. New Dual CK2/HDAC1 Inhibitors with Nanomolar Inhibitory Activity against Both Enzymes

New Dual CK2/HDAC1 Inhibitors with Nanomolar Inhibitory Activity against Both Enzymes

  • ACS Med Chem Lett. 2020 Apr 7;11(5):713-719. doi: 10.1021/acsmedchemlett.9b00561.
Loganathan Rangasamy 1 Irene Ortín 1 José María Zapico 1 Claire Coderch 1 Ana Ramos 1 Beatriz de Pascual-Teresa 1
Affiliations

Affiliation

  • 1 Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925 Alcorcón, Madrid, Spain.
Abstract

Four potent CK2 inhibitors derived from CX-4945 are described. They also provided nanomolar activity against HDAC1, therefore having promising utility as dual-target agents for Cancer. The linker length between the hydroxamic acid and the CX-4945 scaffold plays an important role in dictating balanced activity against the targeted Enzymes. The seven-carbon linker (compound 15c) was optimal for inhibition of both CK2 and HDAC1. Remarkably, 15c showed 3.0 and 3.5 times higher inhibitory activity than the reference compounds CX-4945 (against CK2) and SAHA (against HDAC1), respectively. Compound 15c exhibited micromolar activity in cell-based cytotoxic assays against multiple cell lines.

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