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

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.

SUBMITTER: Rangasamy L

PROVIDER: S-EPMC7236037 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Rangasamy Loganathan L Ortín Irene I Zapico José María JM Coderch Claire C Ramos Ana A de Pascual-Teresa Beatriz B

ACS medicinal chemistry letters 20200407 5

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 inhibito ...[more]

PMID: 32435375

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