Stat3 inhibitors and their anticancer use
Patent Number: US20150232434
Executive Summary:
General Description:
Constitutive activation of STAT3 has been found in a wide variety of cancers, including breast cancer, sarcomas, and other cancers, promoting it as a very attractive therapeutic target. Cytokines, hormones, and growth factors binding to the cell surface receptors can activate the JAK-STAT signaling pathway. The receptors are activated and phosphorylated by JAK kinase(s). Subsequently, the STAT3 monomer is phosphorylated at Tyrosine705 (pTyr705) by the same kinases through its SH2 domain binding to pY loop of the activated receptors, leading to STAT3 homodimer through its SH2 dimerization. The dimerized STAT3 then translocates into the nucleus and binds to DNA, turning on a host of oncogenes. Altogether, these events such as cell proliferation and apoptosis resistance.
This invention relates to compounds useful for STAT inhibition, methods of making same, pharmaceutical compositions comprising same, and methods of treating STAT related diseases using same.
Scientific Progress:
There are no FDA-approved STAT3-targeting drugs. Therefore, more druggable STAT3 inhibitors with higher potency and better bioavailability, such as this invention, are important.
Future Directions:
Strengths:
Weaknesses:
Patent Status:
Patent citations:
https://patents.google.com/patent/US6514986B2/en
https://patents.google.com/patent/US6214880B1/en
Inventor Bio: Chenglong Li
http://pharmacy.osu.edu/research/meet-researcher-chenglong-li-medicinal-chemistry-and-pharmacognosy
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Pending
- Patent Link: https://patents.google.com/patent/US20150330832/
- Research Institute: Ohio State University, Nationwide Children's Hospital
- Disease Focus: STAT3-dependent cancers, including breast cancer and sarcomas
- Basis of Invention: This invention defines compounds useful for STAT inhibition, methods of making same, pharmaceutical compositions comprising same, and methods of treating STAT related diseases using same
- How it works: Compounds inhibit STAT3 activity in disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction
- Lead Challenge Inventor: Chenglong Li
- Inventors: Chenglong Li, Wenying Yu, Jiayuh Lin
- Development Stage: Clinical studies
- Novelty:
- Inhibition of STAT3 phosphorylation and the growth of human cancer cells
- Clinical Applications:
- Effects shown in in vivo in mouse models
General Description:
Constitutive activation of STAT3 has been found in a wide variety of cancers, including breast cancer, sarcomas, and other cancers, promoting it as a very attractive therapeutic target. Cytokines, hormones, and growth factors binding to the cell surface receptors can activate the JAK-STAT signaling pathway. The receptors are activated and phosphorylated by JAK kinase(s). Subsequently, the STAT3 monomer is phosphorylated at Tyrosine705 (pTyr705) by the same kinases through its SH2 domain binding to pY loop of the activated receptors, leading to STAT3 homodimer through its SH2 dimerization. The dimerized STAT3 then translocates into the nucleus and binds to DNA, turning on a host of oncogenes. Altogether, these events such as cell proliferation and apoptosis resistance.
This invention relates to compounds useful for STAT inhibition, methods of making same, pharmaceutical compositions comprising same, and methods of treating STAT related diseases using same.
Scientific Progress:
There are no FDA-approved STAT3-targeting drugs. Therefore, more druggable STAT3 inhibitors with higher potency and better bioavailability, such as this invention, are important.
Future Directions:
- Clinical studies with more results of safety and efficacy and potency
Strengths:
- Compounds useful for STAT inhibition and methods of making them and pharmaceutical compositions comprising these compounds
Weaknesses:
- Mechanism of STAT3 inhibition can be better defined
Patent Status:
- Priority date 2012-08-16
- Filing date 2013-08-16
- Publication date 2015-08-20
Patent citations:
https://patents.google.com/patent/US6514986B2/en
https://patents.google.com/patent/US6214880B1/en
Inventor Bio: Chenglong Li
http://pharmacy.osu.edu/research/meet-researcher-chenglong-li-medicinal-chemistry-and-pharmacognosy