Phase I pharmacokinetic and pharmacodynamic study of triciribine phosphate monohydrate, a small-molecule inhibitor of AKT phosphorylation, in adult subjects with solid tumors containing activated AKT.

Investigational New Drugs
Christopher R GarrettSaïd M Sebti

Abstract

Triciribine phosphate is a potent, small-molecule inhibitor of activation of all three isoforms of AKT in vitro. AKT is an intracellular protein that, when activated, leads to cellular division; it is dysregulated in a large number of malignancies, and constitutively activating AKT mutations are present in a minority of cancers. In this phase I study triciribine phosphate monohydrate (TCN-PM) was administered to subjects whose tumors displayed evidence of increased AKT phosphorylation (p-AKT) as measured by immunohistochemical analysis (IHC). TCN-PM was administered over 30 min on days 1, 8 and 15 of a 28-day cycle. Tumor biopsy specimens, collected before treatment and on day +15, were assessed for p-AKT by IHC and western blot analyses. Nineteen subjects were enrolled; 13 received at least one cycle of therapy, and a total of 34 complete cycles were delivered. One subject was treated at the 45 mg/m(2) dose before the study was closed due to its primary objective having been met. No dose-limiting toxic effects were observed. Modest decreases in tumor p-AKT following therapy with TCN-PM were observed at the 35 mg/m(2) and 45 mg/m(2) dose levels, although definitive conclusions were limited by the small sample size. These prelim...Continue Reading

References

Aug 22, 1995·International Journal of Cancer. Journal International Du Cancer·A BellacosaJ R Testa
Jan 1, 1996·Cancer Chemotherapy and Pharmacology·K HoffmanG N Hortobagyi
Dec 2, 1999·Genes & Development·S R DattaM E Greenberg
Dec 13, 2005·Nature Reviews. Drug Discovery·Bryan T HennessyGordon B Mills
Jun 9, 2006·Cancer Biology & Therapy·Athanassios ArgirisEverett Vokes
Jul 21, 2006·The New England Journal of Medicine·Charles L Sawyers
Jan 28, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Irene M GhobrialPaul G Richardson

❮ Previous
Next ❯

Citations

Jul 9, 2013·European Journal of Medicinal Chemistry·Shi-Hong ZhuangLi-Jiau Huang
May 4, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maria E BalasisSaïd M Sebti
Nov 22, 2013·PloS One·Claire AmiablePierre Alexandre Kaminski
Apr 30, 2011·Future Medicinal Chemistry·Colleen R McNamara, Alexei Degterev
May 7, 2013·Chinese Journal of Cancer·Khurum H KhanDavid Cunningham
Nov 28, 2013·Sarcoma·Christopher L CubittDamon R Reed
May 31, 2011·Cellular Signalling·Ingeborg HersJeremy M Tavaré
Jan 1, 2014·International Journal of Cancer. Journal International Du Cancer·Victor JeannotAmandine Hurbin
Dec 7, 2013·Journal of Hepatology·Matthias S MatterSnorri S Thorgeirsson
Jul 4, 2012·Biochimica Et Biophysica Acta·K Adam Morrow, Lalita A Shevde
Dec 14, 2011·Cancer Biology & Therapy·SubbaRao V MadhunapantulaGavin P Robertson
Oct 15, 2014·Cancer Treatment Reviews·Hanneke StegemanJohan Bussink
Aug 26, 2014·Journal of Cancer Research and Clinical Oncology·Hui Jun LimJia-Lin Yang
Jun 1, 2016·Frontiers in Physiology·Hong Jun KimSang Cheul Oh
Apr 20, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chen HuQiang Xiao
Jun 26, 2013·Nature Reviews. Cancer·Eric W-F LamChuay-Yeng Koo
Oct 9, 2019·Expert Opinion on Investigational Drugs·Maryam Shariati, Funda Meric-Bernstam
Aug 1, 2012·Paediatric Drugs·David BarrettDavid T Teachey
Nov 23, 2019·Expert Opinion on Emerging Drugs·Asaf MaozKoji Matsuo
Nov 26, 2015·World Journal of Gastroenterology : WJG·Shikha Satendra SinghAlan Prem Kumar
May 23, 2018·International Journal of Molecular Medicine·Yong LanYangfang Li
Aug 31, 2020·Medicine in Drug Discovery·Hanxiao YuWenjun Tang
Mar 2, 2021·European Journal of Pharmacology·Ayda Baghery Saghchy KhorasaniDavood Bashash
May 8, 2021·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Shridhar NarayananNarayanan Surendran

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.