STAT3 inhibitor formulation
Inventors
Shoemaker, Robert H. • Lovell, Michael W. • White, Jonathan M. • Gupta, Shanker
Assignees
Glg Pharma LLC • MRIGlobal Inc • US Department of Health and Human Services
Publication Number
US-10913709-B2
Publication Date
2021-02-09
Expiration Date
2038-04-05
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Abstract
Disclosed is a salt prepared from the STAT3 inhibitor known as 2-hydroxy-4-[[2-[[(4-methylphenyl)sulfonyl]oxy]acetyl]amino] benzoic acid and 2-amino-2-(hydroxymethyl)-1,3-propanediol. The salt is soluble in water and stable for extended periods of time. Further provided are pharmaceutical compositions comprising the salt and methods of administering the salt to prevent and treat cancer, such as breast cancer.
Core Innovation
The invention discloses a novel salt formed from the STAT3 inhibitor known as 2-hydroxy-4-[[2-[[(4-methylphenyl)sulfonyl]oxy]acetyl]amino] benzoic acid and 2-amino-2-(hydroxymethyl)-1,3-propanediol. This compound, referred to as Compound 1, exhibits high water solubility and forms stable pharmaceutical compositions. The salt can be crystalline, amorphous, or semi-crystalline and is intended to be highly pure for therapeutic uses.
The problem addressed by this invention is the poor solubility of 2-hydroxy-4-[[2-[[(4-methylphenyl)sulfonyl]oxy]acetyl]amino] benzoic acid in water and ethanol, which makes practical administration of the compound for preventing or treating cancer difficult. This limitation hindered effective delivery of the active agent for therapies targeting cancers associated with increased STAT3 activity.
By providing a stable, highly water-soluble salt form, the invention enables the formulation of pharmaceutical compositions that can be conveniently administered through multiple routes, including oral and intravenous. These compositions facilitate effective methods for preventing and treating cancer, specifically including breast cancer, by improving administration and efficacy through enhanced solubility and stability.
Claims Coverage
The patent includes three independent claims, each presenting a key inventive feature.
A specific salt of STAT3 inhibitor with 2-amino-2-(hydroxymethyl)-1,3-propanediol
A compound of the formula corresponding to the salt formed between 2-hydroxy-4-[[2-[[(4-methylphenyl)sulfonyl]oxy]acetyl]amino] benzoic acid and 2-amino-2-(hydroxymethyl)-1,3-propanediol. - The compound is specifically defined by its chemical structure as provided. - The salt may exist in various physical forms, such as crystalline.
Pharmaceutical composition including the defined salt and a pharmaceutically acceptable carrier
A pharmaceutical composition that comprises the aforementioned salt (Compound 1) and a pharmaceutically acceptable carrier. - The composition is not limited to any specific carrier, allowing for flexibility in formulation, but must include the defined compound.
Methods of preventing and treating cancer using the defined salt
A method of preventing or treating cancer in a subject by administering an effective amount of the defined salt (Compound 1). - The method is applicable to breast cancer prevention (in one independent claim), and to treatment of cancer (in another independent claim). - The cancer to be prevented or treated is characterized by the compound’s efficacy as described, such as cancers having increased STAT3 activity.
In summary, the patent claims cover (1) the novel salt of a specific STAT3 inhibitor with 2-amino-2-(hydroxymethyl)-1,3-propanediol, (2) pharmaceutical compositions incorporating this salt, and (3) methods of using the salt to prevent and treat cancer.
Stated Advantages
The salt form is highly soluble in water, enabling clear and convenient pharmaceutical formulations.
The compound and its compositions are stable for extended periods of time under a range of storage conditions.
The pharmaceutical compositions facilitate improved administration and efficacy for the prevention and treatment of cancer.
The invention enables oral or intravenous administration, with oral administration being preferred.
Documented Applications
Prevention and treatment of cancer, including but not limited to breast cancer, pancreatic cancer, liver cancer, and other types specified in the patent.
Inhibition of STAT3 and/or Ki67 expression in normal and cancerous tissues as a means to prevent cancer onset.
Delay in the onset of DMBA-induced breast cancer in a mouse model supports application in cancer chemoprevention.
Formulation for oral or intravenous administration in pharmaceutical compositions aimed at subjects at risk for, suspected of having, or diagnosed with cancer.
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