33 results about "Stat3 Signaling Pathway" patented technology

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 discloses an application of a compound as a JAK-STAT3 signal passage inhibitor, and particularly relates to an application of a compound with a formula I or pharmaceutically acceptable salt of the compound in the process of preparing an anti-tumor medicament. The application provides a novel treating candidate medicament for a tumor patient, thereby probably further improving the treatment effect on the patient and improving the prognosis of the patient. The compound with the formula I or the pharmaceutically acceptable salt of the compound has the effect on various tumor cells, which indicates that the compound can be used for treating various cancers including cerebral tumor, genitourinary system tumor, lymphatic system tumor, stomach cancer, laryngeal cancer, nasopharyngeal cancer, skin cancer, bone cancer, blood cancer, leukemia, breast cancer and histiocytic lymphoma, non-small cell lung cancer, small-cell lung cancer, lung adenocarcinoma, lung squamous cell cancer, pancreatic cancer, prostatic cancer, liver cancer, epithelial cell cancer and the like. The definition of genes in the formula refers to description for details.

The present invention provides a bifunctional fusion protein targeting VEGF and EGFR and an application of the bifunctional fusion protein. The provided fusion protein can specifically bind epidermalgrowth factor receptor (EGFR) and vascular endothelial growth factor (VEGF). The provided fusion protein provides targeting with exact curative effect and high stability, and synergistically inhibitsEGFR / VEGF(R) pathway. The fusion protein blocks phosphorylation of Akt / Stat3 signaling pathway, thus inhibits angiogenesis or cell growth and has a significant targeting imaging effect and a significant anti-PDAC tumor effect. The provided fusion protein has very strong targeting specificity to induce tumor cell apoptosis and can be used for treatment of malignant tumors.

The invention discloses the use of Worenine as JNK2 kinase inhibitor. The Worenine can specifically combine JNK2 kinase and the two have strong binding ability, and simultaneously inhibit JNK2 activity in a dose-dependent manner. Worenine has good therapeutic activity against psoriasis, which is closely related to the inhibition of JNK, STAT3 signal pathway activation and the expression of psoriasis marker S1007 by Worenine, so it can be used as an active ingredient to prepare drugs for treating psoriasis.

The invention discloses an application of physalin A in preparation of a JAK2-STAT3 signal channel inhibitor and an antitumor drug. The physalin A is a compound with a structure shown in a formula I. The JAK2-STAT3 signal channel inhibitor can inhibit various tumor cells. As the JAK2-STAT3 is abnormally activated to lead to uncontrollable growth of tumor and apoptosis resistance of tumor cells, tumor cell proliferation is further inhibited and tumor cell apoptosis is further induced. The physalin A can be applied to preparation of the antitumor drug. The physalin A is combined with the chemotherapeutic drug (cis-platinum) can remarkably inhibit tumor cell proliferation so as to realize the purpose of enhancing effect and reducing toxicity. Particularly, the physalin A and cis-platinum combined in use to prepare the antitumor drug troches can generate a very strong synergistic effect, and the antitumor drug troches prepared have very good antitumor activity.

The invention discloses the use of methyl berberine as a JNK2 kinase inhibitor. The methyl berberine can specifically bind to the JNK2 kinase and the two have strong binding ability, and at the same time inhibit the activity of JNK2 in a dose-dependent manner. Methyl berberine has good therapeutic activity on psoriasis, which is closely related to methyl berberine inhibiting the activation of JNK and STAT3 signaling pathways and the expression of psoriasis marker molecule S1007, so it can be used as an active ingredient in the preparation of Medicines to treat psoriasis.

The invention discloses an application of physalin A in preparation of a JAK2-STAT3 signal channel inhibitor and an antitumor drug. The physalin A is a compound with a structure shown in a formula I. The JAK2-STAT3 signal channel inhibitor can inhibit various tumor cells. As the JAK2-STAT3 is abnormally activated to lead to uncontrollable growth of tumor and apoptosis resistance of tumor cells, tumor cell proliferation is further inhibited and tumor cell apoptosis is further induced. The physalin A can be applied to preparation of the antitumor drug. The physalin A is combined with the chemotherapeutic drug (cis-platinum) can remarkably inhibit tumor cell proliferation so as to realize the purpose of enhancing effect and reducing toxicity. Particularly, the physalin A and cis-platinum combined in use to prepare the antitumor drug troches can generate a very strong synergistic effect, and the antitumor drug troches prepared have very good antitumor activity.

The subject invention pertains to the treatment of tumors and cancerous tissues and the prevention of tumorigenesis and malignant transformation through the modulation of JAK / STAT3 intracellular signaling. The subject invention concerns pharmaceutical compositions containing cucurbitacin I, or a pharmaceutically acceptable salt or analog thereof, to a patient, wherein the tumor is characterized by the constitutive activation of the JAK / STAT3 intracellular signaling pathway. The present invention further pertains to methods of moderating the JAK and / or STAT3 signaling pathways in vitro or in vivo using cucurbitacin I, or a pharmaceutically acceptable salt or analog therof. Another aspect of the present invention concerns a method for screening candidate compounds for JAK AND / or STAT3 inhibition and anti-tumor activity.

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.

The invention provides a new application of acetylvalerian, in particular to the application of acetylvalerian in the preparation of drugs for preventing and / or treating tumors. The present invention finds that acetylvalerian has obvious inhibitory effect on tumor cells, and the inhibitory effect is verified on cells and animal living bodies. It has been verified that acetylvalerianin can induce the degradation of c-Maf, CCND1, and JAK2 oncoproteins, inhibit Otub1, c-Maf, USP10, and STAT3 signaling pathways, thereby effectively controlling the proliferation of tumor cells and inducing their apoptosis. inhibitory and therapeutic effects. At the same time, as a plant extract, acetylvalerian also has the advantage of low toxicity.

The invention discloses application of recombinant porcine-source IL-6 to medicine preparing. The application of the recombinant porcine-source IL-6 comprises application to preparation of medicine for activating signal channels in human cells, application to preparation of medicine for up regulating expressions of adherence factors or inflammatory cell factors or tissue factors in human cells andapplication to preparation of medicine for regulating expressions of chemotactic factors in human cells; medicine for regulating signal channels or downstream gene expressions in human umbilical veinendothelial cells is provided based on the application, and an active ingredient in the medicine comprises the recombinant porcine-source IL-6. Through research findings, the recombinant porcine-source IL-6 can up regulate expressions of adherence factors ICAM-1, inflammatory cell factors IL-6, chemotactic factors MCP-1 and tissue factors, expressions of chemotactic factors IL-8 are reduced, andSTAT3 signal channels can be activated, and therefore the recombinant porcine-source IL-6 can serve as the active ingredient of the medicine capable of achieving the functions.

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 discloses a function and application of SH2B adapter protein 1 (SH2B1) in myocardial hypertrophy treatment. According to the function and application, the mutual relation between SH2B1 genetic expression and myocardial hypertrophy is determined; the SH2B1 expression rises obviously when the myocardial hypertrophy happens; SH2B1 interference and overexpression adenovirus are used for restraining and promoting cardiomyocyte hypertrophy respectively; the SH2B1 gene defect and overexpression are used for restraining and obviously raising Jak2 / Stat3 signal pathway activation respectively, so that cardiac hypertrophy and fibrosis are restrained and promoted, and the cardiac function can be protected and deteriorated. Hence, the SH2B1 gene can be used as a drug target to be used for screening drugs for protecting the cardiac function and / or preventing, relieving and treating cardiac hypertrophy; the SH2B1 gene can be used as a target gene in gene therapy to be used for designing and preparing the drugs for protecting the cardiac function and / or preventing, relieving and treating cardiac hypertrophy; a new path is provided for cardiac hypertrophy treatment.

STAT3 hyperphosphorylation, dimerization and DNA binding are required for its ability to contribute to malignant transformation. As such, STAT3 has been recognized as a promising target for cancer therapy. Although a number of inhibitors of STAT3-STAT3 dimerization have been reported, molecular ligands that prevent interactions between STAT3 and DNA are very rare. The γ-AApeptide-based one-bead-one-compound (OBOC) combinatorial library was used, and identified γ-AApeptides that can selectively inhibit STAT3 / DNA interaction and suppress the expression levels of STAT3 target genes in intact cells. The results not only validate γ-AApeptides as novel inhibitors of STAT3 signaling pathway, but also demonstrate that in addition to the SH2 domain, the DNA binding domain of STAT3 is targetable for the development of new generation of anti-cancer therapeutics. This also validates the approach of OBOC combinatorial library for the identification of ligands targeting traditionally recognized “undruggable targets”.

The present invention relates to a set of biomarkers, microarrays that provide for detection thereof, an expression signature comprising 16 genes or a subset thereof, and the use thereof in determining the regulation status of IL-6 / STAT3 signaling pathway in a cell sample or subject, as well as compositions for the detection thereof. The regulation status of IL-6 / STAT3 signaling pathway in a cell sample or subject may be assayed based on the level of expression of one or more of these genes. The methods and compositions provided herein may be used to evaluate IL-6 / STAT3 pathway regulation status in a sample; classify a cell sample as having a deregulated or regulated IL-6 / STAT3 signaling pathway; determine whether an agent modulates the IL-6 / STAT3 signaling pathway; predict the response of a subject to an agent that modulates the IL-6 / STAT3 signaling pathway; assign treatment to a subject; and / or evaluate the pharmacodynamic effects of therapies designed to regulate IL-6 / STAT3 pathway signaling. Expression of the biomarkers is preferably determined by RT-PCR using SYBR Green methods, and the expression data analyzed and compared to a control sample by use of the random forest method.

The invention belongs to the field of medicines, and particularly relates to an application of an icaritin hydrate for preparing a medicine capable of inhibiting a STAT3 (Signal Transducer and Activator 3 of Transcription) signal pathway and preventing and curing an oral carcinoma, in particular to the application of the icaritin hydrate of a formula I for preparing the medicine capable of inhibiting the STAT3 signal pathway. The icaritin hydrate of the embodiment of the invention can inhibit the STAT3 and the protein phosphorylation of an upstream pathway JAK2 (Janus Kinase 2) of the STAT3 inoral carcinoma cells, accelerates autophagic vacuole to be increased, accelerates an autophagy-related labelled protein to be transformed to LC3 (light chain)-II from LC3-I, increases the expressionof BECN1 and ATG9 proteins, and reduces the expression of an autophagy-related labelled protein p62 / SQSTM1. The invention takes an amphipathic block high-molecular polymer as a carrier to prepare an icaritin hydrate nanometer medicine preparation, the water solubility of the medicine is enhanced, encapsulation efficiency is 80% and above, an effect on inhibiting the oral carcinoma is better, and in addition, biotoxicity is small.

The invention discloses an STAT (Signal Transducer And Activator Of Transcription)3 signal channel small-molecule inhibitor and application thereof. The inhibitor is expressed in a chemical structural formula which is shown in the specification, wherein R1 is halogenated aryl, R2 is halogenated aryl, R3 is oxygen or sulphur. The inhibitor has functions of effectively inhibiting the multiplication of various tumor cells and inducing the apoptosis of the various tumor cells. The newly developed STAT3 signal channel small-molecule inhibitor not only has a remarkable inhibition effect on the phosphorylation of the STAT3, but also has the remarkable inhibition effect on the IL-6-induced STAT3 activation and the activation of the STAT3 upstream signal CrC and Jak2, and therefore, the multiplication of the various tumor cells can be inhibited and the apoptosis of tumor cells can be induced. Besides, the STAT3 signal channel small-molecule inhibitor has an in-vitro and vivo treatment effect on various tumors of acute and chronic leukemia, multiple myeloma, lymphoma, lung cancer, prostate cancer, cervical cancer and the like.

The invention provides a bifunctional fusion protein targeting VEGF and EGFR and application thereof. The fusion protein provided by the invention can specifically bind epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF). The invention provides a fusion protein targeting and synergistically inhibiting the EGFR / VEGF(R) pathway with definite curative effect and high stability. The fusion protein inhibits angiogenesis or cell growth by blocking the phosphorylation of the Akt / Stat3 signaling pathway. It has a remarkable targeted imaging effect and a remarkable curative effect against PDAC tumors. The fusion protein provided by the invention has a strong effect of targeting and specifically inducing tumor cell apoptosis, and can be used for the treatment of malignant tumors.

The invention discloses an application of physagulin P in preparation of antitumor drug. The physagulin P is a compound, the structure of which is shown as formula I in the specification; the invention firstly finds that the physagulin P can lower the expression level of tumor apoptosis resistance genes XIAP and Mcl-1 so as to further inhibit tumor cell proliferation and induce tumor cell apoptosis through inhibiting phosphorylation of STAT3 kinase 705 tyrosine (Tyr705); the physagulin P can obviously inhibit the growths of a variety of malignant tumor cells, such as stomach cancer, lung cancer, liver cancer, myeloma, breast cancer, and the like. The physagulin P shows excellent anti-tumor activity when being used as an anti-tumor activity containing inhibitor of a new specific STAT3 signaling pathway, especially in conjunction with resveratrol and arsenic trioxide. The formula I is as shown in the specification.