Small molecule inhibitors of STAT3 with anti-tumor activity

Patent metadata

Field	Value
Publication number	US-10226439-B2
Application number	US-201715468460-A
Country	US
Kind code	B2
Filing date	Mar 24, 2017
Priority date	May 19, 2006
Publication date	Mar 12, 2019
Grant date	Mar 12, 2019

Abstract

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.

First claim

We claim:

1. A pharmaceutical composition comprising:
a compound having the chemical structure:

or a pharmaceutically acceptable salt or analog thereof; and a pharmaceutically acceptable carrier.

2. A compound having the chemical structure:

or a pharmaceutically acceptable salt or analog thereof.

3. The compound of claim 2 , wherein the compound has the chemical structure:

or a pharmaceutically acceptable salt thereof.

4. The pharmaceutical composition of claim 1 , wherein the compound has the chemical structure:

or a pharmaceutically acceptable salt thereof.

Assignees

• H Lee Moffitt Cancer Ct & Res
• Univ South Florida
• Univ Central Florida Res Found Inc

Inventors

• Turkson James
• Sebti Said M
• Guida Wayne
• Yip Man Lun
• Lawrence Nicholas
• Lawrence Harshani Rithma
• Greedy Benjamin

Classifications

• G01N33/5088

  of vertebrates · CPC title

• G01N33/5011

  for testing antineoplastic activity · CPC title

• C07C311/19

  to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups · CPC title

• A61K31/18

  Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63) · CPC title

• A61K31/00

  Medicinal preparations containing organic active ingredients · CPC title