ArticleOncogene2002
Interference with PDK1-Akt survival signaling pathway by UCN-01 (7-hydroxystaurosporine).
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
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The trial behind it
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Who cites it
72 citing papers in PubMed, 206 citations in OpenAlex.
- Trial
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- Marine-Derived Bisindoles for Potent Selective Cancer Drug Discovery and Development.Molecules (Basel, Switzerland) · 2024Review
- Metabolic control of induced pluripotency.Frontiers in cell and developmental biology · 2023Review
- Molecular Mechanisms of Anticancer Activity of N-Glycosides of Indolocarbazoles LCS-1208 and LCS-1269.Molecules (Basel, Switzerland) · 2021Article
- Copy number aberrations drive kinase rewiring, leading to genetic vulnerabilities in cancer.Cell reports · 2021Article
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- Silencing PDK1 limits hypoxia-induced pulmonary arterial hypertension in mice via the Akt/p70S6K signaling pathway.Experimental and therapeutic medicine · 2019Article
- Mechanisms of the Metabolic Shift during Somatic Cell Reprogramming.International journal of molecular sciences · 2019Review
- Varicella-Zoster Virus ORF63 Protects Human Neuronal and Keratinocyte Cell Lines from Apoptosis and Changes Its Localization upon Apoptosis Induction.Journal of virology · 2018Article
- FoxO3 an important player in fibrogenesis and therapeutic target for idiopathic pulmonary fibrosis.EMBO molecular medicine · 2018Article
- SAMHD1 modulates in vitro proliferation of acute myeloid leukemia-derived THP-1 cells through the PI3K-Akt-p27 axis.Cell cycle (Georgetown, Tex.) · 2018Article
- SAMHD1 inhibits epithelial cell transformation in vitro and affects leukemia development in xenograft mice.Cell cycle (Georgetown, Tex.) · 2018Article
- Preparation and characterization of (-)-Epigallocatechin-3-gallate (EGCG)-loaded nanoparticles and their inhibitory effects on Human breast cancer MCF-7 cells.Scientific reports · 2017Article
- Natural Products Diversity of Marine Ascidians (Tunicates; Ascidiacea) and Successful Drugs in Clinical Development.Natural products and bioprospecting · 2017Review
- Targeting phosphatidylinositol-3-kinase pathway for the treatment of Philadelphia-negative myeloproliferative neoplasms.Molecular cancer · 2015Review
- Checkpoint kinase 1 negatively regulates somatic hypermutation.Nucleic acids research · 2014Article
- Phase I dose-escalation study of AZD7762, a checkpoint kinase inhibitor, in combination with gemcitabine in US patients with advanced solid tumors.Cancer chemotherapy and pharmacology · 2014Article
- Bimodal regulation of p21(waf1) protein as function of DNA damage levels.Cell cycle (Georgetown, Tex.) · 2014Article
- Phase I study of UCN-01 and perifosine in patients with relapsed and refractory acute leukemias and high-risk myelodysplastic syndrome.Investigational new drugs · 2013Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
3-Phosphoinositide-dependent protein kinase-1 (PDK1) plays a central role in activating the AGC subfamily of protein kinases. In particular, PDK1 plays an important role in the regulation of Akt/PKB survival pathway by phosphorylating Akt on Thr308. Here we show that UCN-01 (7-hydroxystaurosporine), a drug now in clinical trials and with a unique fingerprint pattern, induced dephosphorylation and inactivation of Akt, resulting in the turn-off of the survival signals and the induction of apoptosis. Further analysis revealed that UCN-01-mediated Akt inactivation was caused by inhibiting upstream Akt kinase PDK1 (IC50=33 nM) both in vitro and from cells, but not by suppressing Akt itself or phosphatidylinositide-3-OH kinase. UCN-01-induced PDK1 inhibition was also observed in in vivo murine and human tumor xenografts. Overexpression of active form of Akt diminished the cytotoxic effects of UCN-01, suggesting that UCN-01 may in part exert its cytotoxicity by inhibiting PDK1-Akt survival pathway. Because UCN-01 has already proved to have potent anti-tumor activity in vivo, PDK1-Akt survival pathway is a new, attractive target for cancer chemotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.