39results about How to "Inhibition of signaling pathways" patented technology

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 discloses an SIRP alpha mutant or fusion protein thereof, and application thereof. The SIRP alpha mutant has an amino acid sequence shown as SEQ ID NO. 2-3; the fusion protein comprisesthe SIRP alpha or the mutant thereof, and second protein; the second protein is IgG Fc or His6; the mutant and the fusion protein provided by the invention have high affinity to CD47 and can stop thebinding between the SIRP alpha and the CD47 so to achieve tumor treatment.

The invention belongs to the technical field of biological medicines, and particularly relates to a multi-drug-carrying targeted nanoparticle and a preparation method and application thereof. The multi-drug-carrying targeted nanoparticle is prepared by loading a polyphenol compound, iRhom2 siRNA and TNF-Alpha inhibitor on a gold-coated iron oxide core-shell nanoparticle (GNPs), and the molar ratioof the gold-coated iron oxide core-shell nanoparticle, the polyphenol compound, iRhom2 siRNA and the TNF-Alpha inhibitor is 1:(1 to 3):(1 to 3):(1 to 3). The multi-drug-carrying targeted nanoparticledisclosed by the invention increases the bioactivity and bioavailability of the polyphenol compound, and can effectively prevent and treat related diseases as the result of septicemia caused by listeria monocytogenes.

The invention relates to a sulfonium salt stable targeting HDAC polypeptide drug conjugate and application thereof, a sulfonium salt stable apoptosis-promoting polypeptide is coupled with an HDAC inhibitor to form a stable polypeptide HDAC inhibitor with tumor selective toxicity, the nonspecific toxicity of apoptosis polypeptide chemically stabilized by sulfonium salt is remarkably reduced, the stability of protease is higher, and the tumor selective toxicity of the apoptosis polypeptide is remarkably reduced. When a polypeptide drug conjugate is formed by coupling with an HDAC inhibitor, the polypeptide drug can significantly improve the selective toxicity to tumor cells, and has weak toxicity to normal cells. Cell proliferation, cell apoptosis and cell cycle arrest experiments prove that the polypeptide can effectively inhibit proliferation of malignant liver cancer, has relatively good biological safety and has a potential anti-tumor clinical application prospect.

The invention provides application of ailanthone (AIL) which is shown in a formula (I) and is a monomer of Chinese traditional herbs to preparation of medicines for treating prostatic disease. By a compound, in-vitro and / or in-vivo growth and migration of prostate carcinoma cells can be suppressed obviously, protein expression level of an androgen receptor in the prostate carcinoma cells is reduced, and a signal path of the androgen receptor is suppressed. The compound has a prostate cancer treatment application prospect.

The invention belongs to the field of medicines, and discloses a substituted pyridino imidazole compound as shown in the specification and an application thereof in preparation of a medicine for treating lung cancer. Cell level experiments prove that the compound can inhibit proliferation, migration, invasion and clone formation of lung cancer cells, induce apoptosis of the lung cancer cells and inhibit the phosphorylation level of STAT3; mouse in-vivo experiments show that the compound can inhibit growth and metastasis of lung cancer cells, specifically inhibit an STAT3 signal path, inhibit growth of lung cancer cell transplantation tumors and patient PDX tumors in an animal model, lay a foundation for subsequent new drug research and development, and have important theoretical significance and wide application prospects.

The invention discloses the application of a beta-2-glucoprotein-I of the natural type, the cracking type or the V structure domain deletion mutant type in preparing for a novel drug of restraining the angiogenesis. The test testifies that the natural type beta-2-glucoprotein-I (n beta2GPI), the cracking type beta-2-glucoprotein-I (c beta2GPI) and the V structure domain deletion mutant type beta-2-glucoprotein-I (DI-IV) can restrain the angiogenesis of the endothelial cell. The functional mechanism of the invention is that the invention influences the expression and photophosphorylation of an accepter of an endothelial cell growth factor to retain the signal conducting path of the accepter and retain the lower fifty genetic expressions and further retain the multiplication, the migration and the angiogenesis of the endothelial cell. The invention can provide novel preventing and remedying measures for clinical treatment of the diseases of the angiogenesis, such as the multiplication type retina lesion of the diabetes etc.

The invention discloses the application of a Lefty protein in prohibiting fibering pathologic change of organs, in basic research on preparing the medicine for antagonizing TGF-beta, Nodal, BMP, p38MAPK signal pathways, and in preparing the medicine for curing or preventing fibering pathologic change of organs and tissues of liver, kidney, lung, cardiac muscle, skin, etc. The invention has the functions of prohibiting signal pathways (such as TGF-beta / Smad, Nodal signal pathways) related to fibering diseases and activating protein hydrolytic ferment (such as MMP, gelatingase, etc) capable of prohibiting fibering, is a biological preparation with great potential clinical application value, and can help to further probe into the occurring mechanism of fibering diseases.

The invention belongs to the technical field of medicines, and particularly relates to application of a compound in preparation of a medicine for inhibiting a bacterial quorum sensing system. The invention provides application of a compound in preparation of a medicine for inhibiting a bacterial quorum sensing system. Experiment results show that the 2-(3', 4'-dihydroxyphenyl)-1, 3-piperidine-5-aldehyde can inhibit three signal paths of a Pseudomonas aeruginosa quorum sensing system pqsA, lasB and rhlA and inhibit the activity of the Pseudomonas aeruginosa quorum sensing system without inhibiting the growth of the Pseudomonas aeruginosa. Therefore, the pathogenicity and toxicity of the bacteria are reduced without inhibiting the growth of the bacteria, and the generation of multiple drug resistance of the bacteria is slowed down.

The invention relates to the technical field of immune cell therapy, in particular to an initial immune cell activation and amplification system and application thereof. The invention provides an initial immune cell activation and amplification system. A TGF-beta antagonist is added into an activation culture medium, TGF-beta R on the surface of a T cell in a peripheral blood mono-nuclear cell is competitively combined, the combination of TGF-beta and TGF-beta R is blocked, a TGF-beta mediated signal channel is inhibited, the quantity and function of abnormally increased Treg cells are reduced, the functional activity and amplification capacity of T effector cells and antigen presenting cells are up-regulated, the insufficient number and function decline of initial immune cells caused by negative immune regulation mechanisms such as TGF-beta up-regulated Treg cells are avoided, and high-quality and high-quantity excellent seed cells are provided for later successful preparation of targeted immune cells. The invention also provides a method for activating and amplifying initial immune cells and a method for preparing targeted immune cells.

The invention provides a composition for whitening cosmetics and a preparing method thereof. This composition for whitening cosmetics is prepared from, by weight, 0.1%-0.8% of balanites roxburghii seed oil, 0.1%- 20% of pongamia glabra seed oil, 0.1%- 5% of barley seed extract, 0.1% -5%, a of magnesium ascorbyl phosphate, 0.1%-5% of arbutin and 0.1%-1.5% of protease. The composition for whitening cosmetics has the effect of balanced whitening.

The invention belongs to the technical field of biological medicines, and discloses a biological agent for inhibiting response of cells to inflammatory factor stimulation, the biological agent comprises a PRD peptide fragment and / or a TAD peptide fragment, the amino acid sequence of the PRD peptide fragment is shown as SEQ ID NO: 1, and the amino acid sequence of the PRD peptide fragment is shownas SEQ ID NO: 2. Through a molecular biological analysis method, the PRD peptide fragment is found to be a positive regulation region for inhibiting inflammatory stimuli response in YAP1 protein, andthe TAD peptide fragment is found to be a negative regulation region for inhibiting inflammatory stimuli response in YAP1 protein; both the PRD peptide fragment and the TAD peptide fragment can inhibit signaling pathways of TNF-alpha, IL1-beta and LPS, and the PRD peptide fragment and / or the TAD peptide fragment can be used in diseases caused by excessive cytokines, so that a new way is provided for immunotherapy.

The invention discloses a siRNA composition for inhibiting angiogenesis, which is a composition of a nucleic acid molecule for down-regulating VEGFA expression and a nucleic acid molecule for down-regulating VEGFR3 expression, or a composition of a nucleic acid molecule for down-regulating VEGFR1 expression and a nucleic acid molecule for down-regulating VEGFR2 expression. Or a composition of a nucleic acid molecule for down-regulating the expression of VEGFR1, a nucleic acid molecule for down-regulating the expression of VEGFR2 and a nucleic acid molecule for down-regulating the expression of VEGFR3. The invention can efficiently inhibit the generation of new vessels, including the total length of new vessels, the growth of branch vessels and the generation of vascular intersections; the application prospect of treating the vascular proliferation caused by the gene mutation and the diseases caused by the vascular proliferation is realized.

The invention relates to a novel antibody of an interleukin-23 receptor or an antibody fragment thereof. The antibody or the fragment thereof can be effectively combined with IL-23R and block combination of IL-23R and a human IL-23 alpha / IL-12 beta heterodimer ligand, and has a good application prospect. The antibody or an antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises VH CDR1, VH CDR2 and VH CDR3; the light chain variable region comprises VL CDR1, VL CDR2 and VL CDR3; the VH CDR1 comprises an amino acid sequence shown in SEQ ID NO: 3, 13 or 23; the VH CDR2 comprises an amino acid sequence shown in SEQ ID NO: 4, 14 or 24; the VH CDR3 comprises an amino acid sequence shown in SEQ ID NO: 5, 15 or 25; the VL CDR1 comprises an amino acid sequence shown in SEQ ID NO: 8, 18 or 28; the VL CDR2 comprises an amino acid sequence shown in SEQ ID NO: 9, 19 or 29; and the VL CDR3 comprises an amino acid sequence shown in SEQ ID NO: 10, 20 or 30.

The invention provides a composition for whitening cosmetics and a preparing method thereof. This composition for whitening cosmetics is prepared from, by weight, 0.1%-0.8% of balanites roxburghii seed oil, 0.1%- 20% of pongamia glabra seed oil, 0.1%- 5% of barley seed extract, 0.1% -5%, a of magnesium ascorbyl phosphate, 0.1%-5% of arbutin and 0.1%-1.5% of protease. The composition for whitening cosmetics has the effect of balanced whitening.

The invention discloses a method for preparing the recombinant protein swHO1, extracting the total RNA of the liver tissue of rice field eel, and cloning the coding gene of rice field eel heme oxidase 1 into an expression vector through reverse transcription and PCR amplification to obtain the recombinant expression vector pET ‑HO1; transforming the recombinant expression vector pET‑HO1 into Escherichia coli BL21 (DE3) cells for expression and purification to obtain the recombinant protein swHO1. The application of a recombinant protein swHO1 in the regulation of oxidative stress induced by pathogenic bacteria and the expression regulation of immune-related genes in rice field eel. The invention constructs the prokaryotic expression vector of the eel heme oxidase 1 gene, induces the expression, and obtains the purified recombinant protein swHO1 by affinity chromatography. The rice field eel heme oxidase 1 prepared by the invention has the functions of improving the antioxidant capacity in the serum tissue treated with pathogenic bacteria and improving the expression of liver immune-related genes.

The invention discloses a GPR1 antagonistic polypeptide and a derivative and application thereof and particularly relates to a GPR1 antagonistic polypeptide shown in SEQ ID No.1-7 and a derivative thereof. The derivative of the binding peptide is a product obtained in the mode that conventional modification is conducted on a GPR1 binding peptide amino acid side chain group and an amino terminal ora carboxyl terminal of a GPR1 antagonistic polypeptide fragment or a product obtained in the mode that a label for detection or purification of polypeptide or protein is linked to the GPR1 antagonistic polypeptide. The binding peptide and the derivative thereof can be combined with GPR1 in vitro, by stopping combination of chemerin and GPR1, increase of the cAMP concentration is promoted, the (Ca2+) influx caused by chemerin is inhibited, effective micromolecule treatment drugs are provided for diseases, such as breast cancer, of high-expression GPR1 receptors, and the GPR1 antagonistic polypeptide can be widely applied in the fields of medicine and biology.

The invention discloses a GPR1 antagonistic polypeptide and a derivative and application thereof and particularly relates to a GPR1 antagonistic polypeptide shown in SEQ ID No.1-5 and a derivative thereof. The derivative of the binding peptide is a product obtained in the mode that conventional modification is conducted on a GPR1 binding peptide amino acid side chain group and an amino terminal ora carboxyl terminal of a GPR1 antagonistic polypeptide fragment or a product obtained in the mode that a label for detection or purification of polypeptide or protein is linked to the GPR1 antagonistic polypeptide. The binding peptide and the derivative thereof can be combined with GPR1 in vitro, by stopping combination of chemerin and GPR1, increase of the cAMP concentration is promoted, the (Ca2+) influx caused by chemerin is inhibited, effective micromolecule treatment drugs are provided for diseases, such as breast cancer, of high-expression GPR1 receptors, and the GPR1 antagonistic polypeptide can be widely applied in the fields of medicine and biology.

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 polypeptide inhibitor. The amino acid sequence structure of the polypeptide inhibitor is shown in the specification. The invention also provides application of the polypeptideinhibitor in preparation of a medicament for inhibiting LSD1 enzyme activity. The polypeptide provided by the invention can be covalently bound with cysteine (Cys360) near an LSD1 enzyme activity pocket, so that the effect of inhibiting LSD1 protease activity is achieved, and the polypeptide inhibitor can be used for in-vivo anti-tumor treatment.

The invention discloses a GPR1 antagonistic polypeptide and a derivative and application thereof and particularly relates to a GPR1 antagonistic polypeptide shown in SEQ ID No.1-4 and a derivative thereof. The derivative of the binding peptide is a product obtained in the mode that conventional modification is conducted on a GPR1 binding peptide amino acid side chain group and an amino terminal ora carboxyl terminal of a GPR1 antagonistic polypeptide fragment or a product obtained in the mode that a label for detection or purification of polypeptide or protein is linked to the GPR1 antagonistic polypeptide. The binding peptide and the derivative thereof can be combined with GPR1 in vitro, by stopping combination of chemerin and GPR1, increase of the cAMP concentration is promoted, the (Ca2+) influx caused by chemerin is inhibited, effective micromolecule treatment drugs are provided for diseases, such as breast cancer, of high-expression GPR1 receptors, and the GPR1 antagonistic polypeptide can be widely applied in the fields of medicine and biology.

The invention discloses a GPR1 antagonistic polypeptide and a derivative and application thereof and particularly relates to a GPR1 antagonistic polypeptide shown in SEQ ID No.1-7 and a derivative thereof. The derivative of the binding peptide is a product obtained in the mode that conventional modification is conducted on a GPR1 binding peptide amino acid side chain group and an amino terminal ora carboxyl terminal of a GPR1 antagonistic polypeptide fragment or a product obtained in the mode that a label for detection or purification of polypeptide or protein is linked to the GPR1 antagonistic polypeptide. The binding peptide and the derivative thereof can be combined with GPR1 in vitro, by stopping combination of chemerin and GPR1, increase of the cAMP concentration is promoted, the (Ca2+) influx caused by chemerin is inhibited, effective micromolecule treatment drugs are provided for diseases, such as breast cancer, of high-expression GPR1 receptors, and the GPR1 antagonistic polypeptide can be widely applied in the fields of medicine and biology.

The invention relates to the technical field of immune cell therapy, in particular to an initial immune cell activation expansion system and its application. The invention provides an initial immune cell activation and expansion system. TGF-β antagonists are added to the activation medium to competitively bind to TGF-βR on the surface of T cells in peripheral blood mononuclear cells to block TGF-β and TGF The combination of ‑βR inhibits the signaling pathway mediated by TGF‑β, down-regulates the number and function of abnormally increased Treg cells, up-regulates the functional activity and expansion ability of T effector cells and antigen-presenting cells, and avoids the up-regulation of Treg cells due to TGF-β Insufficient number and decreased function of "initial immune cells" caused by such negative immune regulation mechanism provide high-quality and high-quantity excellent seed cells for the successful preparation of targeted immune cells in the later stage. The invention also provides a method for activating and expanding initial immune cells and a method for preparing targeted immune cells.

The invention discloses a GPR1 antagonistic polypeptide and a derivative and application thereof and particularly relates to a GPR1 antagonistic polypeptide shown in SEQ ID No.1-7 and a derivative thereof. The derivative of the binding peptide is a product obtained in the mode that conventional modification is conducted on a GPR1 binding peptide amino acid side chain group and an amino terminal ora carboxyl terminal of a GPR1 antagonistic polypeptide fragment or a product obtained in the mode that a label for detection or purification of polypeptide or protein is linked to the GPR1 antagonistic polypeptide. The binding peptide and the derivative thereof can be combined with GPR1 in vitro, by stopping combination of chemerin and GPR1, increase of the cAMP concentration is promoted, the (Ca2+) influx caused by chemerin is inhibited, effective micromolecule treatment drugs are provided for diseases, such as breast cancer, of high-expression GPR1 receptors, and the GPR1 antagonistic polypeptide can be widely applied in the fields of medicine and biology.

The invention discloses a GPR1 antagonistic polypeptide and a derivative and application thereof and particularly relates to a GPR1 antagonistic polypeptide shown in SEQ ID No.1-7 and a derivative thereof. The derivative of the binding peptide is a product obtained in the mode that conventional modification is conducted on a GPR1 binding peptide amino acid side chain group and an amino terminal ora carboxyl terminal of a GPR1 antagonistic polypeptide fragment or a product obtained in the mode that a label for detection or purification of polypeptide or protein is linked to the GPR1 antagonistic polypeptide. The binding peptide and the derivative thereof can be combined with GPR1 in vitro, by stopping combination of chemerin and GPR1, increase of the cAMP concentration is promoted, the (Ca2+) influx caused by chemerin is inhibited, effective micromolecule treatment drugs are provided for diseases, such as breast cancer, of high-expression GPR1 receptors, and the GPR1 antagonistic polypeptide can be widely applied in the fields of medicine and biology.

The invention provides an application of 20(S)-ginsenoside-Rg3 in reversing drug resistance of glioma cells to chemotherapeutic drugs. Researches find that 20(S)-ginsenoside-Rg3 inhibits expression ofan MGMT gene by inhibiting a Wnt / beta-catenin signal pathway and inhibiting LncRNA NKILA, significantly reverses MGMT mediated drug resistance of glioma cells to temozolomide, promotes apoptosis of tumor cells, and plays a very positive role in treatment of glioma patients.

The invention discloses a GPR1 antagonistic polypeptide and a derivative and application thereof and particularly relates to a GPR1 antagonistic polypeptide shown in SEQ ID No.1-5 and a derivative thereof. The derivative of the binding peptide is a product obtained in the mode that conventional modification is conducted on a GPR1 binding peptide amino acid side chain group and an amino terminal ora carboxyl terminal of a GPR1 antagonistic polypeptide fragment or a product obtained in the mode that a label for detection or purification of polypeptide or protein is linked to the GPR1 antagonistic polypeptide. The binding peptide and the derivative thereof can be combined with GPR1 in vitro, by stopping combination of chemerin and GPR1, increase of the cAMP concentration is promoted, the (Ca2+) influx caused by chemerin is inhibited, effective micromolecule treatment drugs are provided for diseases, such as breast cancer, of high-expression GPR1 receptors, and the GPR1 antagonistic polypeptide can be widely applied in the fields of medicine and biology.

The invention discloses application of an anti-EGFR (epidermal growth factor receptor) scFv:: FTH1 / FTH1 protein nanoparticle in preparation of a preparation for resisting triple negative breast cancer. The anti-EGFR scFv:: FTH1 / FTH1 protein is formed by compounding an anti-EGFR scFv:: FTH1 protein and an FTH1 protein. Compared with commercial anti-EGFR monoclonal cetuximab, EGFR and a signal channel thereof can be better down-regulated under the condition of the same administration dosage, and a more remarkable inhibition effect on proliferation of tumor cells expressing EGFR and growth of tumors of tumor-bearing mice is achieved, so that a better anti-tumor effect is shown, the cetuximab has relatively high safety in a living body, and the anti-EGFR scFv:: FTH1 / FTH1 protein provides a wide prospect for the application of EGFR target-based protein nano-drugs.

The present invention provides a polypeptide inhibitor, whose amino acid sequence structure is as follows: The present invention also provides the use of the above-mentioned polypeptide inhibitor in the preparation of a drug for inhibiting LSD1 enzyme activity. The polypeptide of the invention can be covalently combined with the cysteine ​​(Cys360) near the active pocket of the LSD1 enzyme, thereby inhibiting the activity of the LSD1 protease, and can be used for anti-tumor treatment in vivo.

The invention discloses a preparation method and use of baicalein-7-methyl ether derivatives. The baicalein-7-methyl ether derivatives have a general formula shown in the description. In the general formula, R1 represents hydroxyl and R2 represents a C1-C3 straight chain nitrogen-containing compound, a nitrogen-containing heterocyclic compound or an aryl or ester group compound. The baicalein-7-methyl ether derivatives can substantially inhibit leukemia cell propagation and viability and realizes multi-target inhibition of a leukemia cell signal path so that leukemia cell apoptosis is induced and leukemia treatment is realized.