STAT3 small-molecule inhibitor and its application

Abstract

The invention discloses a STAT3 small-molecule inhibitor and its application, and the STAT3 inhibitor takes an N'-(1-(2,4 dihydroxy phenyl)ethylidene) benzoyl hydrazine derivative or its pharmacologically acceptable salt shown in a formula (1) or a formula (1a) as an effective component. In the formula, R1 and R2 on A ring can be hydroxyl, methoxy carboxyl and ester, and B can be an annular or a chain state. The STAT3 small-molecule inhibitor has selectivity and high activity, According to a three-grade structural design, biosynthesis and reconstructing optimization of STAT3, then a fluorescence polarization method and a CCK-8 method are employed for detecting activity and researching the mechanism on inhibition of tumor cells growth and promotion of differentiation apoptosis, so that effect of the STAT3 small-molecule inhibitor on prevention and control of tumor formation and tumor treatment can be described.

Description

technical field [0001] The invention relates to the field of tumor drugs, in particular to an active small molecule inhibitor designed according to the tertiary structure of signal transduction and transcription factor 3 (STAT3). Background technique [0002] Signal transducer and transcription factor 3 (STAT3) belongs to the STATs family. There are seven members of this family, STAT1-STAT7, which are encoded by different genes, among which STAT1, STAT3, and STAT5 are highly homologous. The STATs family is stimulated by cell growth factors such as EGFR, IL-6, PDGF, etc. to undergo tyrosine phosphorylation to mediate physiological functions such as cell growth, differentiation, migration, and apoptosis. Studies have shown that excess phosphorylated STAT3 can be detected in prostate cancer, breast cancer, head and neck cancer, ovarian cancer, melanoma, and myeloma, while the level of phosphorylated STAT3 in normal epithelial cells is significantly lower. [0003] STAT3 consis...

AI Technical Summary

Problems solved by technology

However, peptide inhibitors have poor cell permeability, easy metabolism, and poor bioavailability. Kinase inhibitors cannot completely inhibit the activity of the downstream STAT3 pathway, while non-peptide small molecule inhibitors have limited inhibitory activity and there is no known STAT3 inhibitor. Therefore, the development of new selective and highly active STAT3 inhibitors is a huge challenge on the one hand and a major opportunity to overcome tumors on the other hand

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