AI Article Synopsis
- Researchers continued their study on anti-cancer agents targeting Nur77 by designing and synthesizing new compounds, particularly 5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole-2-carboxamide derivatives.
- Among these, compound 8b was found to be effective against various cancer cell lines, including liver cancer, with lower toxicity compared to the known compound celastrol.
- 8b demonstrated strong Nur77-binding activity and induced cancer cell death through specific mechanisms involving Nur77, showing promise for further development as a therapy for hepatocellular carcinoma.
Article Abstract
Encouraged by our previous findings and in continuation of our ongoing study project in designing and synthesis of novel Nur77-targeting anti-cancer agents, a series of 5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole-2-carboxamide derivatives were designed, synthesized and biologically evaluated as potent Nur77 modulators. Among synthesized compounds, 8b maintained good potency against different liver cancer cell lines and other types of cancer cell lines while exhibiting lower toxicity than the positive compound celastrol. Moreover, 8b displayed excellent Nur77-binding activity, superior to the lead compound 10g and comparable to the reference compound celastrol. The cytotoxic action of 8b towards cancer cells was associated with its induction of Nur77-mitochondrial targeting and Nur77-dependent apoptosis. Notably, 8b has good in vivo safety and anti-hepatocellular carcinoma (HCC) activity. Altogether, this study reveals that 8b is a novel Nur77 modulator with great promise for further research.
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| http://dx.doi.org/10.1016/j.ejmech.2022.114849 | DOI Listing |
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