T-17, a novel cyclin-dependent kinases/histone deacetylases dual inhibitor, induces cancer cells death through cell cycle arrest and apoptosis.
Drug Dev Res
; 83(7): 1578-1588, 2022 11.
Article
en En
| MEDLINE
| ID: mdl-35844039
ABSTRACT
Combination of cyclin-dependent kinases (CDKs) and histone deacetylases (HDACs) inhibitors may have statistical synergy in suppressing cancer cell proliferation. Herein, a novel CDKs/HDACs dual inhibitor T-17 was rationally designed, synthesized, and evaluated. Our results demonstrated that T-17 concurrently exhibited potent and balanced inhibitory activity against CDKs (IC50 = 18.0 nM) and HDACs (IC50 = 6.6 nM) and also displayed good cell viability inhibitory effect on four cancer cell lines. Meanwhile, T-17 blocked the MDA-MB-231 and A549 cell cycle at G1 phase and S phase, respectively. In addition, T-17 induced MDA-MB-231 cells apoptosis and inhibited the HDACs and CDKs mediated signaling pathways. Finally, we also found that T-17 had good antitumor activity in vivo. In summary, these results indicated that T-17 would be a promising lead compound which deserves further research.
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Neoplasias
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Antineoplásicos
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Año:
2022
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Article