University of Central Florida Research Foundation Inc

University of South Florida

H. Lee Moffitt Cancer Center and Research Institute, Inc.

University of Toronto

Yale University

University of Hawai'i

James Turkson

Said M Sebti

Richard Jove

Nicholas James Lawrence

Andrew D Hamilton

Harshani Lawrence

Wayne Charles Guida

Patrick Thomas Gunning

Man Lun Yip

Benjamin Greedy

Swadeshmukul Santra

Hua Yu

Jay W Palmer

Heidi Kay

Marcus A Tius

Dianqing Sun

Astha Malhotra

Peibin Yue

Patrick Gunning

Sina Haftchenary

Christine Brotherton-Pleiss

Padmavathy Tallury

Leng Chee Chang

Francisco Javier Lopez Tapia

Supakit Wongwiwatthananukit

Ui Joung Youn

The subject invention concerns a compound and compositions having activity as an inhibitor of Stat3 protein and methods of using the compound and compositions. In one embodiment, a compound of the invention has the structure shown in formula I, formula II, or formula III. The subject invention also concerns methods of using the compounds and compositions of the invention.

Platinum compounds that inhibit constitutive STAT3 signaling and induce cell cycle arrest and apoptosis of malignant cells

The present disclosure provides pharmaceutical compositions comprising 2-arylsulfonamido-N-arylacetamide derivatized Stat3 inhibitors and certain pharmaceutically acceptable salts thereof, and methods of their use.

2-arylsulfonamido-N-arylacetamide derivatized STAT3 inhibitors

The present invention concerns compounds, compositions containing these compounds, and methods of using these compounds and compositions as inhibitors of Stat3 signaling, Stat3 dimerization, Stat3-DNA binding, Stat5-DNA binding, and/or aberrant cell growth in vitro or in vivo, e.g., as anti-cancer agents for treatment of cancer, such as breast cancer. The compounds of the invention include, but are not limited to, NSC 74859 (S3I-201), NSC 42067, NSC 59263, NSC 75912, NSC 11421, NSC 91529, NSC 263435, and pharmaceutically acceptable salts and analogs of the foregoing. Other non-malignant diseases characterized by proliferation of cells that may be treated using the compounds of the invention, but are not limited to, cirrhosis of the liver; graft rejection; restenosis; and disorders characterized by a proliferation of T cells such as autoimmune diseases, e.g., type 1 diabetes, lupus and multiple sclerosis. The invention further includes an in-vitro screening test for the presence of malignant cells in a mammalian tissue; a method of identifying inhibitors of constitutive Stat3 activation, Stat3-DNA binding, Stat5-DNA binding, and/or Stat3 dimerization; and a method of identifying anti-cancer agents.

Small molecule inhibitors of STAT3 with anti-tumor activity

The present disclosure provides a method of purifying pharmaceutical compositions consisting essentially of STAT3 inhibitors from a mixture of compounds, pharmaceutical compositions comprising STAT3 inhibitors used to inhibit STAT3 in tumor cells, and certain pharmaceutically acceptable salts thereof, and methods of use.

Sesquiterpenoid STAT3 inhibitors

In one aspect, the invention relates to substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs as inhibitors of STAT protein

The present disclosure provides pharmaceutical compositions comprising Stat3 inhibitors and certain pharmaceutically acceptable salts thereof, and methods of use.

STAT3 inhibitors

The present invention concerns compounds, compositions containing these compounds, and methods of using these compounds and compositions as inhibitors of Stat3 signaling, Stat3 dimerization, Stat3-DNA binding, Stat5-DNA binding, and/or aberrant cell growth in vitro or in vivo, e.g., as anti-cancer agents for treatment of cancer, such as breast cancer. The compounds of the invention include, but are not limited to, NSC 74859 (S31-201), NSC 42067, NSC 59263, NSC 75912, NSC 11421, NSC 91529, NSC 263435, and pharmaceutically acceptable salts and analogs of the foregoing. Other non-malignant diseases characterized by proliferation of cells that may be treated using the compounds of the invention, but are not limited to, cirrhosis of the liver; graft rejection; restenosis; and disorders characterized by a proliferation of T cells such as autoimmune diseases, e.g., type 1 diabetes, lupus and multiple sclerosis. The invention further includes an in-vitro screening test for the presence of malignant cells in a mammalian tissue; a method of identifying inhibitors of constitutive Stat3 activation, Stat3-DNA binding, Stat5-DNA binding, and/or Stat3 dimerization; and a method of identifying anti-cancer agents.

A stabilized chitosan-based nanoparticle is provided having a chitosan polymer and a hydrophilic dispersing agent. In the stabilized nanoparticle, chains of the chitosan polymer electrostatically interact with chains of the hydrophilic dispersing agent to form an entangled network between the chitosan polymer and the hydrophilic dispersing agent. The stabilized chitosan-based nanoparticle has optimal particle integrity and stability properties under physiological conditions.

Stabilized chitosan-based nanoparticles and methods for making the same

An activatable nanoprobe is provided having a core component and an active agent associated with the core component via a bond configured to be cleaved upon exposure to an endogenous compound.

Activatable nanoprobes for intracellular drug delivery

Disclosed herein are compounds derived from a chemical structure according to the formula (I) wherein X comprises oxygen or sulfur, Rcomprises a phenyl or naphthyl group, Rcomprises an amide group and Rcomprises a phosphate group. The disclosed compounds demonstrate inhibitory activity against STAT3, a protein found in certain tumor tissues and which promotes cellular overproliferation and resistance to apoptosis. The invention includes compositions containing the disclosed compounds, as well as methods of treatment therewith. 

Inhibitors of STAT3

The present invention provides compounds S3I-201.1066 (Formula 1) and S3I-201.2096 (Formula 2) as selective Stat3 binding agents that block Stat3 association with cognate receptor pTyr motifs, Stat3 phosphorylation and nuclear translocation, Stat3 transcriptional function, and consequently induced Stat3-specific antitumor cell effects in vitro and antitumor response in vivo.

Growing community of inventors

Orlando, FL, United States of America

James Turkson