triciribine phosphate (PTX-200)

Triciribine (TCN) is a tricyclic nucleoside. 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.

Using a nitroblue tetrazolium dye reduction assay and real-time quantitative PCR using NB4 APL cells, we revealed that, PD169316, SB203580, SB202190 (p38 MAPK inhibitor), and triciribine (TCN) (Akt inhibitor) potently increased the expression of CD11b. Real-time PCR analysis demonstrated that components of these pathways including IL1β, CD3D, IL5RA, ITGA6, CD44, ITGA2B, CD37, CD9, CSF2RA, and IL3RA, were upregulated by TCN-induced differentiation. Collectively, we identified TCN as a novel myeloid cell differentiation inducer, and trials of TCN for APL and non-APL leukemia are worthy of exploration in the future.

R54 impairs Tregs function in primary RCC patients targeting PTEN/PI3K/AKT pathway, reducing TSDR demethylation and FOXP3 and DNMT1 expression. Thus, CXCR4 targeting is a strategy to inhibit Tregs activity in the RCC tumour microenvironment.

P1/2, N=33, Completed, Prescient Therapeutics, Ltd. | Recruiting --> Completed | Trial completion date: Dec 2021 --> Mar 2024 | Trial primary completion date: Dec 2021 --> Oct 2023

Collectively, the current findings demonstrated that ZNF275 serves as a sufficiently predictive indicator of the therapeutic effectiveness of the combined treatment of triciribine and cisplatin on cervical cancer. Combining triciribine with cisplatin greatly broadens the therapeutic options for cervical cancer expressing high ZNF275, but further research is needed to confirm these results.

No abstract available

In this study, we established a triciribine-resistant cell line from HEC-151 cells. Our data suggest that the mechanism of drug resistance in endometrial cancer cells is attributed to the increased expression of ABC transporters.

P1/2, N=40, Recruiting, Prescient Therapeutics, Ltd. | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021

P1/2, N=34, Terminated, Prescient Therapeutics, Ltd. | Active, not recruiting --> Terminated; criteria for continuing enrollment in Phase 2 portion was not met

The present study was based on the high expression of Hsp90 during heat stress (HS) and involved inducing higher expression of Hsp90 using aspirin in mouse hearts...Protection by Hsp90 was weakened by blocking Akt activation using Triciribine, which could not be recovered by normal initiation of the PKM2 pathway. Furthermore, increased Hsp70 levels induced by Akt activation in myocardial cells may flow into the blood to resist heat stress. The results provided in vivo mechanistic evidence that in myocardial cells, Hsp90 resists heat stress via separate activation of the Akt‑Bcl‑2 and PKM2‑Bcl‑2 signaling pathways, which contribute toward preserving cardiac function and mitochondrial homeostasis.

P1/2, N=34, Active, not recruiting, Prescient Therapeutics, Ltd. | Trial completion date: Dec 2022 --> Feb 2020

P1/2, N=40, Recruiting, Prescient Therapeutics, Ltd. | Trial completion date: Dec 2019 --> Dec 2020 | Trial primary completion date: Dec 2019 --> Dec 2020