83 results about "Stat3 inhibitor" patented technology

Disclosed herein are compositions for inhibition of Stat, particularly Stat3. Disclosed herein are compositions comprising cell permeable Stat3 inhibitors. Compositions may comprise peptides, polypeptides, antibodies, nucleic acids, vectors, and host cells for making, using, assaying, and evaluating Stat3 inhibitors. Disclosed herein are methods for making and using the disclosed compositions.

The invention relates to small molecules which function as inhibitors of Stat3. The invention also relates to the use of these compounds for inducing cell death and sensitizing cells to the induction of cell death by anti-cancer drugs.

Small molecule inhibitors of Stat3 and their derivatives are disclosed. Also described are methods to inhibit cell growth by use of Stat3 inhibitors, and the use of Stat3 inhibitors for the prevention and / or treatment of cancer. Further, inhibitors of Stat3 that also do not inhibit Stat1 are described as well as their derivatives. Methods of screening additional compounds for Stat3 inhibition activity and / or non-inhibition of Stat1 activity are also described herein.

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.

Methods of enhancing antitumor activity of an immune cell comprising contacting the immune cell with a Stat3 inhibitor are described. Also described are methods of killing a tumor cell or inhibiting tumor growth in a subject comprising contacting an immune cell of the subject with a Stat3 inhibitor.

Small molecule inhibitors of Stat3 and their derivatives are disclosed. Also described are methods to inhibit cell growth by use of Stat3 inhibitors, and the use of Stat3 inhibitors for the prevention and / or treatment of cancer. Further, inhibitors of Stat3 that also do not inhibit Stat1 are described as well as their derivatives. Methods of screening additional compounds for Stat3 inhibition activity and / or non-inhibition of Stat1 activity are also described herein.

The invention discloses an STAT3 small molecular selective inhibitor and a preparation method and applications thereof, and the STAT3 small molecular selective inhibitor comprises four structure general formulae as shown in formula I, formula II, formula III and formula IV. The preparation comprises the following steps: allowing 2-phenyl substituted quinoline-4-carboxylic acid thionyl chloride or oxalyl chloride to react to generate substituted acyl chloride, reacting with substituted arylamine to generate substituted quinoline-4-amide derivatives. The applications comprise an application in the preparation of medicaments for treating cancers related to abnormally-activated STAT3 pathway, and an application in the preparation of antitumor medicaments where the STAT3 small molecular selective inhibitor is used as an inhibitor of the STAT3 signal pathway. The STAT3 inhibitor of the invention is a small molecular selective inhibitor; based on results obtained by detecting its effect on cancer cells and evaluating its activity, the small molecular STAT3 selective inhibitor of the invention is applicable to the development of related cancer-treatment medicaments, has quite wide applications, and has very good medicine curative effect. The small molecular STAT3 selective inhibitor of the invention has various types, easily available raw materials, a simple preparation method, high product purity, high yield, and strong practicality.

The invention relates to the application of compounds possessing STAT3 inhibitor activity shown in general formula I, isomers and a drug compound containing the compounds and isomers in the prevention or treatment of malignant tumors, AIDS and inflammations and the termination of unexpected pregnancies or the application of tool drugs used for studying the growth, proliferation, differentiation and apoptosis of tumors as well as STAT3-related signaling pathways.

The invention discloses an STAT3 (Signal Transducer and Activator of Transcription 3)-targeting small molecular compound as well as a preparation method and application thereof. The STAT3 inhibitor is a compound shown as a general formula I in the specification, wherein R<1> is 5-chloro-2-hydroxyphenyl, (E)-3-(6-bromo-2-pyridine)-2-cyan or 4-(2-phenylquinoline); R<2> is hydrogen or C1-C6 linear alkyl or branched alkyl. The compound has the advantages that the proliferation and the survival of various tumor cells of breast cancer, lung cancer, liver cancer, cervical cancer, prostate cancer and the like can be remarkably inhibited; the STAT3 signal channel of the tumor cells is inhibited; therefore, the tumor cell apoptosis is induced and the effect of treating the tumor diseases is achieved.

Provided are STAT3 inhibitors and methods of treating inflammation or a hyperproliferative disease such as, e.g., cancer. In some aspects, compounds may be used to treat breast cancer, a head / neck cancer, a lung cancer, a prostate cancer, or pancreatic cancer.

The invention belongs to the technical field of medicine, and particularly relates to an application of a compound separated and extracted from burdock to serving as an STAT3 inhibitor. The compound I can be used for a medicine composition for treating triple negative breast cancer. The compound I and docetaxel are combined into a compound preparation for treating triple negative breast cancer for use. Phosphorylation of STAT3 is remarkably inhibited through burdock aglycone in a cell and animal tumor-bearing model, and the burdock aglycone is free of obvious toxic and side effects on other normal tissues. The application has the advantages of being proper in dosage, remarkable in curative effect, clear in action target, small in toxic and side effect and the like, and has the broad anticancer application prospect in clinic. The compound preparation has the low toxic and side effects. As the toxicity of the burdock aglycone is quite low, and the burdock aglycone and the docetaxel are used as a composition, under the condition that the same anticancer curative effect is achieved, the dosage of the docetaxel can be remarkably decreased, and therefore the toxic and side effects brought by the docetaxel can be further reduced.

Methods of modulating the INF-induced STAT3 activation in a patient in need-thereof are provided for the treatment of disease. The methods comprise the step of administrating to a patient the combination of a therapeutically effective amount of interferon including INF-α and / or INF-β in combination with a STAT3 inhibitor.

The invention discloses a benzothiazine-1,1-dioxides having a structure of Formula I as a new type of highly efficient STAT3 small molecule inhibitor, which is used for developing antineoplastic drugs.

The invention belongs to the technical field of medicine and pharmacy, and discloses an application of a micromolecule compound WZ-2-033 shown as below to medicines for treating breast cancer and stomach cancer. The compound can restrain proliferation, clone formation, migration and invasion of breast cancer cells and stomach cancer cells, and can induce apoptosis of the breast cancer cells and the stomach cancer cells. The compound exerts effects through influencing an STAT3 signal channel, can reduce the phosphorylation level (Y705) of the STAT3, can reduce STAT3 dimer formation, can reduceDNA combining capacity and transcriptional activity of the STAT3, and can further reduce the expression level of STAT3 target genes c-Myc, Bcl-xL and Mcl-1 so as to restrain activation of STAT3 signals and restrain the growth of the breast cancer cells and the stomach cancer cells. In an animal model, the compound can restrain the growth of stomach cancer cell transplanted tumors and has favorableapplication prospects.

The invention discloses application of physalis pubescens lactone B in preparing anti-cancer drugs. The physalis pubescens lactone B is a compound having a structure as shown in formula I; the physalis pubescens lactone B is combined with cis-platinum in use to prepare anti-cancer drugs; the compound having the structure as shown in the formula I serves as a novel STAT3 inhibitor, and simultaneously acts as a chemotherapy synergist which, combined with the cis-platinum, can take a synergistic action to greatly improve an anti-cancer activity. Test results show that the physalis pubescens lactone B, as a novel STAT3 inhibitor, has an anti-cancer activity and can be used for preparing anti-cancer drugs. When combining the physalis pubescens lactone B and the cis-platinum in use, a strong synergistic action is generated; compared to single use of the cis-platinum, the combination of the physalis pubescens lactone B and the cis-platinum shows stronger anti-cancer activity; the anti-cancer drugs prepared by the combination of the physalis pubescens lactone B and the cis-platinum are favorable for market promotion and have wide application prospect. The formula I is as shown in the specification.

The present invention includes methods for the treatment of autoimmune disorders such as autism, schizophrenia, and type 1 diabetes. Flavonoids, luteolin, diosmin, and diosmin's aglycone form, diosmetin, were found to inhibit activation / phosphorylation of STAT3 induced by IL-6 in cultured neuronal cells. Furthermore, mice treated with diosmin showed a significant reduction of autistic phenotype induced by IL-6 through inhibition of STAT3 activation.

The abnormal adjustment and control of an Stat3 (signal transducer and activator of transcription 3) signal transduction system generally exist in canceration cell strains. The invention provides a compound EGCG (epigallocatechin gallate) which is an effective Stat 3 inhibitor. The Stat 3 inhibitor can be applied to preparation of cancer therapy medicines containing endogenous activated Stat3 signal paths.

The invention discloses a micromolecule selective depressant for STAT3 (Signal transducer and activator of transcription 3), as well as a preparation method and an applications thereof. The micromolecule selective depressant for the STAT3 comprises a structural formula I and a structural formula II; the preparation method comprises the steps of: taking alkaline as a catalyst in DMSO (Dimethyl sulfoxide) or DMF (Dimethylformamide) solvent, and carrying out cyclization on N-bis(methylthio) methylene-arylsulfonamide and 3.3'-dihydroxyl benzidine in the DMSO; and the applications are shown in aspects of preparing medicaments for treating cancers related to an abnormally activated STAT3 pathway and anti-tumor medicaments as an STAT3 signal pathway depressant. The STAT3 depressant is a micromolecule selective depressant, can be used for developing related cancer treating medicaments by determining action on cancer cells to evaluate the active result, thus having a wide range of application,as well as good curative effect of the medicaments. The varieties of the micromolecule selective depressants for the STAT3 are multiple, the preparation method is simple, the product purity is high, the yield is high and the practicability is strong.

The invention belongs to the fields of medicinal chemistry and pharmacotherapeutics, and discloses a quinolone derivative as shown in a formula I in the description or pharmaceutically acceptable salt or ester thereof. The invention also discloses application of the quinolone derivative or the pharmaceutically acceptable salt or ester thereof in preparation of an STAT3 inhibitor or in preparation of a medicine for preventing and / or treating tumor-related diseases. Pharmacological experiments prove that the quinolone derivative or the pharmaceutically acceptable salt or ester thereof can achieve the anti-tumor purpose by inhibiting proliferation of tumor cells and inducing apoptosis of the tumor cells, and the quinolone derivative or the pharmaceutically acceptable salt or ester thereof has an anti-tumor effect and is relatively low in toxicity. The quinolone derivative can be combined with a target protein STAT3SH2 structural domain, so that formation of an STAT3 homodimer is mediated, and a JAK-STAT3 cellular pathway is selectively inhibited.

The invention belongs to the technical field of medicines, and particularly relates to new application of guanosine, in particular to new application of guanosine in preparation of medicines for treating asthma or inhibitors of MAPK, NF-kappa B and STAT3. The invention aims to solve the problem that safer and more effective asthma treatment medicines need to be developed urgently in the prior art.It is found that in an in-vitro THP-1-derived macrophage inflammation model, guanosine inhibits generation of a proinflammatory factor IL-6 by inhibiting activation of MAPK and NF-kappa B; in an asthma mouse model, guanosine reduces OVA-IgE of mouse plasma, reduces generation of IL-4, IL-6 and IL-13, relieves airway high reactivity, and relieves lung tissue cell infiltration, airway inflammationand collagen deposition. In addition, the expression levels of p-p38 MAPK, p-p65 NF-kappa B, p-I kappa B alpha and p-STAT3 proteins in lung tissues of mice in a guanosine treatment group are obviouslylower than those in an asthma model group. Therefore, the invention provides application of guanosine in preparation of a p38 MAPK inhibitor, a p65 NF-kappa B inhibitor, an STAT3 inhibitor or an asthma treatment drug.

The invention discloses application of traditional Chinese medicine monomer toosendanin as an STAT3 inhibitor in preparation of osteosarcoma resisting drug. The anti-tumor activity of the toosendanin and a specific action mechanism thereof are discussed from various aspects of external, internal and biochemical molecular level. Mechanism research shows that the activity of STAT3 is inhibited through the toosendanin by directly targeting STAT3; an external experiment result shows that the toosendanin can inhibit proliferation of various osteosarcoma cells lines, induce cell apoptosis, stop cell invasion and reverse epithelium-mesenchymal cell transformation of osteosarcoma; in vivo, the toosendanin can inhibit growth of osteosarcoma and transfer and prolong the lifetime of tumor-bearing mice; and finally, by a human-derived osteosarcoma model, it discovers that the toosendanin remarkably inhibits growth of the human-derived osteosarcoma. The result shows that the toosendanin can be used as the STAT3 inhibitor to prepare the drug for resisting the osteosarcoma.

The invention discloses a new use of a natural product Eupalinolide J; the natural product Eupalinolide J can be used as an STAT3 inhibitor, and furthermore, the natural product Eupalinolide J is used as a raw material for preparing anti-breast cancer drugs. The invention discloses an inhibitory effect of the Eupalinolide J on STAT3 in triple-negative breast cancer cells for the first time; the compound is proved to be an efficient STAT3 inhibitor, and provides a theoretical basis for new triple-negative breast cancer targeting therapy and clinic entering of the Eupalinolide J.

The invention discloses application of a pyrimidazole-type STAT3 inhibitor in preparation of a medicine capable of delaying or reversing acquired resistance to TKIs, wherein the pyrimidazole-type STAT3 inhibitor is a substituted pyrimidazole compound with a structure as follows (including chiral isomers R and S). As a small-molecule compound, the pyrimidazole-type STAT3 inhibitor disclosed by theinvention is capable of delaying or reversing occurrence of acquired drug resistance in EGFR-TKIs cancer treatment, as well as inhibiting the acquired resistance to the EGFR-TKIs in NSCLC patients soas to enhance sensitivity of the cancer to the EGFR-TKIs, thereby overcoming the disadvantage of liable occurrence of resistance of the EGFR-TKIs and improving curative effects of the EGFR-TKIs; and thus, the pyrimidazole-type STAT3 inhibitor has good application prospects.

The invention provides composition of matter comprising at least one STAT3 inhibiting moiety or any vehicle, matrix, nano- or micro-particle comprising the same, associated with at least one mitochondrial targeting moiety. The invention further provides compositions comprising said mitochondrial-targeted STAT3 inhibitor, methods and uses thereof in inhibiting mast cell degranulation and in treating disorders induced by activation of MC.

The invention discloses a heteroaromatic amide compound and a preparation method and application thereof. According to the heteroaryl amide compound provided by the invention, a preliminary activity research shows that the compound has selectivity to STAT3 and also has very strong tumor cell proliferation inhibition activity; the compound can be used as a series of novel STAT3 inhibitors and can be used for preparing drugs for treating corresponding diseases. The compound has obvious killing effect on human cancer cells, especially human breast cancer cell line MDA-MB-231, human prostate cancer cell line PC-3 and human prostate cancer cell line DU-145, has the potential of being prepared into novel antitumor drugs, and has better market prospect.