Structure-Based Design of Conformationally Constrained, Cell-Permeable STAT3 Inhibitors
- 10 March 2010
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Medicinal Chemistry Letters
- Vol. 1 (2), 85-89
- https://doi.org/10.1021/ml100010j
Abstract
We report herein the structure-based design of a class of conformationally constrained, potent, cell-permeable small-molecule inhibitors to target the SH2 domain in STAT3. Compound 11 (CJ-1383) binds to STAT3 with a Ki value of 0.95 μM, dose-dependently inhibits cellular STAT3 signaling and cancer cell growth, and induces apoptosis in the MDA-MB-468 cancer cell line with constitutively activated STAT3.Keywords
This publication has 26 references indexed in Scilit:
- Synthesis of Phosphatase-Stable, Cell-Permeable Peptidomimetic Prodrugs That Target the SH2 Domain of Stat3Organic Letters, 2009
- Conformationally Constrained Peptidomimetic Inhibitors of Signal Transducer and Activator of Transcription 3: Evaluation and Molecular ModelingJournal of Medicinal Chemistry, 2009
- Design, synthesis, and evaluation of peptidomimetics containing Freidinger lactams as STAT3 inhibitorsBioorganic & Medicinal Chemistry Letters, 2009
- Targeting Protein–Protein Interactions: Suppression of Stat3 Dimerization with Rationally Designed Small‐Molecule, Nonpeptidic SH2 Domain BindersChemBioChem, 2008
- STAT3 as a target for inducing apoptosis in solid and hematological tumorsCell Research, 2008
- Solid-phase synthesis of Stat3 inhibitors incorporating O-carbamoylserine and O-carbamoylthreonine as glutamine mimicsBioorganic & Medicinal Chemistry Letters, 2007
- The STATs of cancer — new molecular targets come of ageNature Reviews Cancer, 2004
- Phosphotyrosyl Peptides Block Stat3-mediated DNA Binding Activity, Gene Regulation, and Cell TransformationPublished by Elsevier BV ,2001
- STAT proteins: novel molecular targets for cancer drug discoveryOncogene, 2000
- The role of STATs in transcriptional control and their impact on cellular functionOncogene, 2000