Signaling effect, combinations, and clinical applications of triciribine
1Division of Laboratory Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Abstract:
Triciribine (TCN) is a tricyclic nucleoside. Its synthesis was first described in 1971. Subsequent studies have indicated that TCN plays a role in inhibiting DNA synthesis and was revealed to possess a higher selectivity for Akt. Although a single dose of TCN demonstrated limited activity in solid tumors at the clinical level, combinations of TCN with various agents, such as specific inhibitors, tyrosine kinase inhibitor dasatinib, ErbB inhibitor tipifarnib, IGF1-R inhibitor NVP-AEW541, mTORC1 inhibitor RAD-001, TNF-related apoptosis-inducing ligand, PPARγ agonist, 1,25(OH)2D3, gemcitabine, and paclitaxel, have been reported to be efficient against various malignancies such as pancreatic, breast, prostate cancer, insulinoma, gut neuroendocrine tumor, and hepatocellular carcinoma at the preclinical level. Other than malignancies, through Akt inhibition activity, TCN has also been demonstrated potential for treating lung injuries, including those encountered in COVID-19 infections.
Insights
Triciribine (TCN), a nucleoside, inhibits DNA synthesis and targets Akt. Combinations show promise against various cancers and lung injuries, including those from COVID-19.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Triciribine (TCN) is a tricyclic nucleoside synthesized in 1971.
- TCN inhibits DNA synthesis and exhibits selectivity for Akt.
- Single-dose TCN has limited clinical activity in solid tumors.
Purpose of the Study:
- To review the efficacy of TCN in combination therapies for various malignancies.
- To explore TCN's potential in treating non-cancerous conditions like lung injuries.
Main Methods:
- Literature review of preclinical and clinical studies involving TCN.
- Analysis of TCN's Akt inhibition mechanism.
- Evaluation of combination therapies with TCN and other agents.
Main Results:
- Preclinical studies show TCN combinations are effective against pancreatic, breast, prostate cancer, insulinoma, gut neuroendocrine tumors, and hepatocellular carcinoma.
- TCN demonstrates potential for treating lung injuries, including those associated with COVID-19, via Akt inhibition.
Conclusions:
- TCN combination therapies offer a promising strategy for treating diverse malignancies.
- TCN's Akt inhibition provides a therapeutic avenue for lung injuries and viral infections.
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