STAT3 Inhibitor Salt Formulation for Cancer Treatment
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Solution Overview
Problem
The compound 2-hydroxy-4-[[2-[[(4-methylphenyl)sulfonyl]oxy]acetyl]amino] benzoic acid, known as NSC-74859 or S3I-201, is a potent inhibitor of STAT3 but is poorly soluble in water and ethanol, making practical administration for cancer treatment challenging.
Innovation Solution
A novel salt of 2-hydroxy-4-[[2-[[(4-methylphenyl)sulfonyl]oxy]acetyl]amino] benzoic acid with 2-amino-2-(hydroxymethyl)-1,3-propanediol is developed, enhancing water solubility and stability, forming a clear pharmaceutical composition for effective cancer treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If 2-hydroxy-4-[[2-[[ (4-methylphenyl) sulfonyl] oxy] acetyl] amino] benzoic acid is used as a cancer treatment agent, then STAT3 inhibition and cancer treatment efficacy are improved, but water solubility deteriorates
Solution Approach 1:
The patent applies parameter changes by converting the compound from its acid form to a salt form (specifically the disodium salt), which fundamentally alters its solubility parameters. This chemical modification transforms the molecule's properties to achieve high water solubility while maintaining STAT3 inhibition efficacy, directly resolving the contradiction between treatment effectiveness and solubility
Solution Approach 2:
The patent introduces a salt-forming intermediary (sodium hydroxide or other bases) that reacts with the acid compound to create a soluble salt form. This intermediary enables the transformation from an insoluble acid to a soluble salt, serving as a bridge that maintains the active ingredient's therapeutic function while improving its dissolution properties for practical administration
2Reliability
If 2-hydroxy-4-[[2-[[ (4-methylphenyl) sulfonyl] oxy] acetyl] amino] benzoic acid is used as a cancer treatment agent, then STAT3 inhibition and cancer treatment efficacy are improved, but formulation stability deteriorates
Solution Approach 1:
The patent applies parameter changes by transforming the compound into a salt form, which alters its chemical stability parameters. The salt form exhibits enhanced stability in aqueous formulations compared to the acid form, allowing for stable storage and administration while maintaining the compound's ability to inhibit STAT3 and treat cancer effectively
3Reliability
If 2-hydroxy-4-[[2-[[ (4-methylphenyl) sulfonyl] oxy] acetyl] amino] benzoic acid is used as a cancer treatment agent, then cancer treatment efficacy is improved, but ease of administration deteriorates
Solution Approach 1:
The patent applies parameter changes by converting the compound to a salt form with high water solubility, which fundamentally improves its ease of administration. The soluble salt form can be readily dissolved in aqueous carriers for oral or parenteral administration, eliminating the practical difficulties associated with administering the insoluble acid form while preserving the compound's cancer treatment efficacy
Data Source
Figure 1A~1D
Figure 2~3
Figure 4~5
AI summary
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.