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Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine…
- M. Blaskovich, Jiazhi Sun, A. Cantor, J. Turkson, R. Jove, S. Sebti
- Biology, ChemistryCancer research
- 15 March 2003
The suppression of phosphotyrosine STAT3 levels resulted in the inhibition of STAT3 DNA binding and STAT3-mediated but not serum response element-mediated gene transcription, giving strong support for pharmacologically targeting the JAK/STAT3 signaling pathway for anticancer drug discovery.
Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity
- K. Siddiquee, Shumin M. Zhang, J. Turkson
- Chemistry, BiologyProceedings of the National Academy of Sciences
- 1 May 2007
Findings strongly suggest that the antitumor activity of S3I-201 is mediated in part through inhibition of aberrant Stat3 activation and provide the proof-of-concept for the potential clinical use of Stat3 inhibitors such as S3i-201 in tumors harboring aberrantStat3.
Akt/Protein Kinase B Signaling Inhibitor-2, a Selective Small Molecule Inhibitor of Akt Signaling with Antitumor Activity in Cancer Cells Overexpressing Akt
The discovery of a small molecule Akt pathway inhibitor, Akt/protein kinase B signaling inhibitor-2 (API-2) is reported, providing strong evidence for pharmacologically targeting Akt for anticancer drug discovery.
Discovery of a Novel Shp2 Protein Tyrosine Phosphatase Inhibitor
NSC-87877 is identified as the first PTP inhibitor capable of inhibiting Shp2 PTP in cell cultures without a detectable off-target effect and provides the first pharmacological evidence that Shp 2 mediates EGF-induced Erk1/2 MAP kinase activation.
Targeting protein prenylation for cancer therapy
This Review discusses the mechanisms by which FT and GGT1 inhibitors (FTIs and G GTIs, respectively) affect signal transduction pathways, cell cycle progression, proliferation and cell survival, and strategies to overcome this.
Ras CAAX Peptidomimetic FTI-277 Selectively Blocks Oncogenic Ras Signaling by Inducing Cytoplasmic Accumulation of Inactive Ras-Raf Complexes (*)
The results demonstrate that FTI-277 blocks Ras oncogenic signaling by accumulating inactive Ras/Raf complexes in the cytoplasm, hence preventing constitutive activation of the MAPK cascade.
The Phosphoinositide 3-OH Kinase/AKT2 Pathway as a Critical Target for Farnesyltransferase Inhibitor-Induced Apoptosis
It is demonstrated that FTI-277 inhibits phosphatidylinositol 3-OH kinase (PI 3-kinase)/AKT2-mediated growth factor- and adhesion-dependent survival pathways and induces apoptosis in human cancer cells that overexpress AKT2.
Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin,…
It is demonstrated that this highly potent and selective novel class of non-thiol-containing peptidomimetic inhibitors of FTase inhibits human tumor growth in whole animals and that combination therapy with cytotoxic agents is more beneficial than monotherapy.
Cucurbitacin Q: a selective STAT3 activation inhibitor with potent antitumor activity
- J. Sun, M. Blaskovich, R. Jove, S. Livingston, D. Coppola, S. Sebti
- Chemistry, MedicineOncogene
- 21 February 2008
The authors have identified errors and addressed them in the article entitled ‘Cucurbitacin Q: a selective STAT3 activation inhibitor with potent antitumor activity’.
Inhibition of the prenylation of K-Ras, but not H- or N-Ras, is highly resistant to CAAX peptidomimetics and requires both a farnesyltransferase and a geranylgeranyltransferase I inhibitor in human…
Soft agar experiments demonstrated that in all the human tumor cell lines tested inhibition of K-Ras prenylation was not necessary for inhibition of anchorage-independent growth, and that inhibition of human tumor growth in soft agar does not require inhibition of oncogenic K- Ras processing.