20 results about "Notch signalling pathway" patented technology

The invention discloses an application of a POGLUT1 gene in reversing senescence of skin fibroblasts. According to the application, by down-regulating expression of POGLUT1 in skin fibroblasts, SA-beta-Gal activity and expression of senescence marker genes p16, p21 and p53 can be reduced, the cell apoptosis number is reduced, and the anti-inflammatory capacity of HSFs is improved, so that the effect of reversing senescence of the skin fibroblasts is achieved. The invention discloses POGLUT1 as a core regulatory gene of MSCs for reversing skin aging, and a molecular regulatory network of the POGLUT1 in a skin aging process through a Notch signal channel, and clarifies a potential molecular mechanism of MSCs for reversing skin aging. The invention provides a new molecular target for clinically treating skin aging related diseases, also provides a new theoretical basis for understanding the effect of MSCs in skin aging, and also lays an important experimental foundation for clinically developing an anti-aging treatment strategy based on MSCs or POGLUT1 targets.

The invention belongs to the field of biological medicines, and relates to a pharmaceutical composition and application thereof in preparation of medicines for preventing and treating hepatitis B virus. Comprising a nucleic acid drug and a carrier for loading the nucleic acid drug, the carrier can specifically target liver Kupffer cells, the nucleic acid drug is mRNA, and a gene sequence for coding the mRNA comprises nucleotide sequences shown as SEQ ID NO: 1 and SEQ ID NO: 2. The pharmaceutical composition provided by the invention can specifically activate Notch signal channels of Kupffer cells, and can play a role in treating and preventing hepatitis B; meanwhile, the anti-HBV effect of the pharmaceutical composition depends on the participation of Kupffer cells, and the pharmaceutical composition becomes a potential novel strategy for clinical treatment of chronic hepatitis B.

The present invention provides the application of oroxindin B in the preparation of drugs for preventing and / or treating atherosclerosis, belonging to the fields of biotechnology and pharmaceutical technology. The present invention discovers through research that oroxindin B can be used to prepare Notch signaling pathway inhibitors. The oroxindin B can inhibit the protein of the key transcription factor RBPJ of the Notch pathway, change the expression / function of Notch cofactors or effector factors, thereby inhibiting the expression of downstream genes, and further achieving the purpose of inhibiting the development of AS and reducing the generation of atherosclerotic plaques. The oroxindin B has good application prospects in the preparation of drugs for preventing and / or treating atherosclerosis.

The invention discloses a novel application of a recombinant protein preparation ANXA2 as a NOTCH agonist. The ANXA2 can be used as an agonist of NOTCH2 and NOTCH4, plays a treatment role in NOTCH signal channel related diseases, provides a research tool for the NOTCH signal channel related diseases, and has a wide application prospect.

The present application relates to the field of biological medicine, in particular to a mutant protein related to Notch signal pathway and use thereof. The mutant protein provided by the present application is a mutant Notch1 protein, a mutant DLL4 protein or a mutant JAG1 protein. The mutant protein related to Notch signal pathway provided by the present application: the mutant Notch1 protein has strong activation signal after binding with its ligands DLL4 and JAG1, and is used for regulating the disorder of Notch signal pathway, and can provide a basis for the occurrence mechanism research and development of treatment strategies of developmental disorders, cancers and other diseases.

The invention relates to a nasal mucosa mesenchymal stem cell culture medium and application thereof, and belongs to the technical field of stem cell culture.The nasal mucosa mesenchymal stem cell culture medium is composed of a basic culture medium, an additive and additive factors, and the additive factors comprise one or more of pyruvic acid, a Notch signaling pathway inhibitor and a brain-derived neurotrophic factor; according to the culture medium, the proliferation efficiency and differentiation potential of the human nasal mucosa mesenchymal stem cells are remarkably improved.

The present invention relates to pharmaceutical combinations comprising a kinase inhibitor and a NOTCH signaling pathway inhibitor and their use in a method for the prevention, delay of progression or treatment of cancer in a subject.

The present application relates to the technical field of biological diagnosis, and particularly relates to a mutant gene set for tumor molecular typing and application thereof, wherein the mutant gene set comprises 82 mutant genes including DNA methylation modification related genes, histone modification related genes, chromatin remodeling related genes, TCR signal pathway related genes, PI3K-AKT signal pathway related genes, JAK-STAT signal pathway related genes, immune escape related genes, P53 signal pathway related genes, tumor suppressor genes and NOTCH signal pathway related genes. The mutant gene set can be used for molecular typing, targeted therapy and overall survival prediction of intranodal peripheral T-cell lymphoma. The mutant gene set is verified by clinical trials, and is suitable for all primary and relapsed PTCL patients, relapsed or refractory peripheral T-cell lymphoma umbrella study based on genomics typing and PTCL patients receiving different treatment schemes, and has a very wide application range.

The invention discloses a computer-aided drug screening method based on ANXA2 and NOTCH2 / NOTCH4, and relates to a drug screening method based on ANXA2 and NOTCH2 / NOTCH4. The invention provides a brand-new method, system or equipment for screening drugs based on ANXA2 and NOTCH2 / NOTCH4, provides a tool for new drug development and clinical application for NOTCH signal channel related diseases, and has a wide application prospect.

To provide a multispecific antigen-binding molecule which enables Notch signaling pathway activation in a cell of interest in a cell anchorage-dependent manner, a method for producing the multispecific antigen-binding molecule, and a pharmaceutical composition comprising such a multispecific antigen-binding molecule as an active ingredient for activating the Notch signaling pathway in a cell of interest.SOLUTION: The present invention provides multispecific antigen-binding molecules comprising a first antigen-binding moiety that specifically binds to a Notch receptor on a first target cell and a second antigen-binding moiety that specifically binds to an anchor antigen on a second target cell.SELECTED DRAWING: None

The present invention relates to the treatment of cancer and particularly of lung cancer. In the present study, the inventors analyzed the role of the Notch pathway in EGFR-driven lung adenocarcinoma (LUAD) using complex genetic mouse models and patient derived xenografts. They found that, similarly to KRAS-driven LUAD, EGFR-driven LUAD shows both Notch pathway hyperactivation and addiction to its activity. Importantly, combination of EGFR tyrosine Kinase Inhibitors (TKIs) with Notch inhibition re-sensitizes LUAD cells harboring gatekeeper mutations EGFRT790M or EGFRC797S to gefitinib and osimertinib, respectively. Moreover, they show that pSTAT3, which is known to increase upon EGFR TKI treatment, directly binds to the HES1 promoter and represses HES1 expression. Finally, high HES1 expression levels correlate with shorter progression free survival and its expression increases upon progression in EGFR mutated patients under TKI treatment. Thus, the present invention relates to a combination of a tyrosine-kinase inhibitor (TKI) against epidermal growth factor receptor (EGFR) and an inhibitor of the Notch signalling pathway for use in the treatment of a cancer in a subject in need thereof.

The invention discloses application of fibroblast-MMP11 in pancreatic cancer angiogenesis and tumor cell heterogeneity and metastasis, relates to the technical field of biological medicine, and discloses application of fibroblast-MMP11 in pancreatic cancer angiogenesis and tumor cell heterogeneity and metastasis. Preferably, the drug targets the FbMMP11 or the VEGF and NOTCH signal channels activated by the FbMMP11. According to the application of the fibroblast-MMP11 as the pancreatic cancer diagnosis marker, prognosis and metastasis risks of patients are evaluated by detecting the expression level of the FbMMP11. The invention relates to a pharmaceutical composition for inhibiting angiogenesis and metastasis of pancreatic cancer. The pharmaceutical composition comprises an inhibitor targeting FbMMP11 and a VEGF / NOTCH signaling pathway blocker. In the invention, the molecular basis of the FbMMP11 subgroup for promoting tumor matrix fibrosis through high expression of collagen synthesis genes such as COL1A1 and INHBA is defined; secondly, a new mechanism that FbMMP11 promotes tumor angiogenesis by activating VEGF and NOTCH signal pathways in EnCOL15A1 endothelial cells is disclosed.

The application discloses application of MC1R, in particular, application of an agent for inhibiting MC1R in preparation of a drug for treating colorectal cancer, and belongs to the field of biological medicines. In vitro experiments show that overexpression of MC1R in a colorectal cancer cell line promotes cell proliferation and migration, and inhibits ferroptosis by down-regulating ACSL4 expression, while knockdown of MC1R has an opposite effect. In vivo experiments also find that xenograft tumor volume and weight formed by colorectal cancer cells with knockdown of MC1R are reduced, it is found that MC1R activates a Notch signal pathway, causes ACSL4 expression to be inhibited, thereby inhibiting ferroptosis and further blocking cell growth and migration; high expression of MC1R in colorectal cancer is related to poor prognosis, and is negatively correlated with the ferroptosis level. Targeting MC1R can provide a new strategy for enhancing ferroptosis of colorectal cancer, and provides an important clue for development of targeted therapy for colorectal cancer.

Disclosed herein use of an inhibitor of ATR / CHK1 pathway in treating a NOTCH pathway-related disease, particularly, a disease caused by an aberrant NOTCH signaling pathway, especially a cancer associated with mutation and / or activation of NOTCH. Also disclosed herein a method for treating a NOTCH pathway-related disease, particularly, a disease caused by an aberrant NOTCH signaling pathway, especially a cancer associated with mutation and / or activation of NOTCH with an inhibitor of ATR / CHK1 pathway.

The application belongs to the field of biological medicine, and relates to a kind of pharmaceutical composition and its application in preparation of the drug for preventing and treating hepatitis B virus. Including nucleic acid drug and the carrier loaded with the nucleic acid drug, the carrier can specifically target liver kupffer cell, and the nucleic acid drug is mRNA, and the gene sequence coding the mRNA includes the nucleotide sequence shown in SEQ ID NO:1 and SEQ ID NO:2. The pharmaceutical composition provided by the application can specifically activate the Notch signal pathway of kupffer cell, and can play the effect of treating and preventing hepatitis B. Meanwhile, the anti-HBV effect of the pharmaceutical composition depends on the participation of kupffer cell, and becomes a new type of strategy for potential clinical treatment of chronic hepatitis B.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a small-molecule inhibitor in preparation of a medicine for treating glioblastoma. The small molecule inhibitor is WAY-324631, and the CAS number of the small molecule inhibitor is 438618-43-0. The research discovers that WAY-324631 can stop interaction between KAT7 and CTCF, reduce acetylation of CTCF and inhibit activation of NOTCH signal channels by targeting a binding site between KAT7 and CTCF, so that the malignant progression of glioblastoma is slowed down. In addition, the small-molecule inhibitor is combined with TMZ for use, so that the sensitivity of GBM cells to TMZ can be remarkably improved. The invention provides a new target and strategy for treatment of GBM.

The invention discloses serine and L-lysine salts as shown in a formula I or a formula II as well as a preparation method and application of the serine and L-lysine salts in nervous system disease autism spectrum disorders, the synthesized serine and L-lysine salts are lower in heavy metal content and higher in stability compared with serine or lysine, and the application of the serine and L-lysine salts in nervous system disease autism spectrum disorders is promoted. According to the present invention, the problems of high heavy metal content and unstable storage when the two amino acids are separately used are overcome, the serine and the L-lysine form the salt, and the NICD and Hes1 protein expression is significantly reduced, such that the two serine and the L-lysine salt can effectively inhibit the abnormal activation of the Notch signal channel;

The invention provides a multi-factor composition for regulating a WNT-NOTCH signal channel to improve the tooth forming ability of odontogenic stem cells, which is characterized in that an expression vector replaced by a promoter is firstly constructed, then the promoter-positive odontogenic stem cells are screened by the vector, and then the odontogenic stem cells are continuously stimulated by the multi-factor composition, so that the odontogenic ability of the odontogenic stem cells is improved, and the odontogenic ability of the odontogenic stem cells is improved. Therefore, the tooth forming capability of the odontogenic stem cells is improved. The dental implant has the excellent effects that the dental restoration capability is enhanced, the biocompatibility and the integration are improved, the regeneration of a natural tooth structure is promoted, the dental pulp infection risk is reduced, the long-term stability of treatment is improved, the discomfort of a patient is reduced, the recovery time of the patient is shortened, and the dental implant has wide clinical application potential.

Disclosed are a compound and use for and a method for treating aberrant Notch signaling diseases and as checkpoint kinase 1 inhibitors, or as double targeting inhibitors of both NOTCH1 and CHK1, and especially for cancer, using a heteroaromatic compound of general formulae (I), (II), (III), and (IV), or their pharmaceutically acceptable salt, a stereoisomeric, isotopic, tautomeric or polymorphic form, or prodrug thereof.