30 results about "Nuclear receptor" patented technology

Disclosed herein are methods of assessing changes of expression in patients' nervous systems of molecules responsive to treatments modulating nuclear receptors for retinoid X (RXR alpha, beta, or gamma), Nurr1(NR4A2) nuclear receptors, Nur77 (NR4A1) nuclear receptors, dopamine active transporter (DAT), or dopa decarboxylase (DDC), for nervous system disorders or conditions related to these molecules.

The invention relates to the technical field of biological medicine, in particular to a truncated variant of a nuclear receptor LBD region and application of the truncated variant. According to the truncated variant of the nuclear receptor LBD structural domain provided by the invention, at least one amino acid is deleted at the C terminal. The ER, PR and GR truncated variants can induce transcriptional activation of a downstream signal channel under the condition that NTD is deleted, and a brand new treatment target is provided for patients with cancers such as prostatic cancer, breast cancer, endometrial cancer, acute lymphocytic leukemia, lymphoma, pancreatic cancer and lung cancer.

This application discloses a method for predicting the quantitative activity of endocrine disruptors, relating to the field of virtual screening of endocrine disruptors. The method includes: acquiring in vitro experimental data of nuclear receptors and removing duplicate data, as well as removing compound sets that do not contain the simplified molecular linear input canonical (SMILES) representation; using a molecular fingerprinting method to extract the primary, secondary, and tertiary structural features of the compounds. For each compound cluster, a quantitative prediction model based on machine learning or quantitative read-across is constructed to predict the quantitative activity value of the compound. Addressing the low efficiency of existing methods for predicting the quantitative activity of endocrine disruptors, this application extracts multi-level structural features of the compounds and constructs corresponding quantitative prediction models for compound structural clusters of different sizes. Through molecular docking and molecular dynamics simulations, the interaction mechanism between endocrine disruptors and nuclear receptors is studied from a structural biology perspective, thus improving efficiency.

The application discloses an application of a nuclear receptor target gene in preparation of a biological preparation for blocking activation of diapause larvae, and relates to the field of biotechnology and parasite prevention and control. According to two nuclear receptor targets of Haemonchus contortus HCON_00101910 (regulating activity of worms) and HCON_00023750 (regulating development of larvae), the two nuclear receptor targets are combined with host progesterone and estradiol and are activated, constitute a key signal path in the spring activation process of diapause larvae, and have no homologous genes in mammals, and the safety is excellent. By constructing specific shRNA lentivirus vectors (the silencing efficiency is all greater than or equal to 60%) targeting the two genes, single target or double target synergistic intervention is realized, and the activity-development double key links of worms in the host body can be specifically blocked. The application provides a new paradigm of preventive prevention and control with high specificity and green safety, and provides core technical support for solving the seasonal epidemic problem of blood fluke disease.

The present relates to novel nuclear receptor related 1 (Nurr1) modulators, preferably agonists, having a new carboxylic acid / carboxamide bioisosteric moiety Y and being optionally deuterated, pharmaceutical formulations comprising them, a process for their preparation and their use as medicament, alone or in combination with one or more additional agents, for treating of various diseases, wherein the modulation of Nurr1 is beneficial in such diseases (e.g. multiple sclerosis or Parkinson's disease).

The invention belongs to the technical field of biochemical detection, and discloses a rapid new pollutant screening method based on PPAR or ER protein affinity binding, PPAR or ER protein with a His tag is selectively adsorbed to a Ni-magnetic bead carrier, and then a new pollutant is screened according to the principle of affinity binding of a nuclear receptor and ligand small molecules. Effect substances with binding activity are specifically captured from a complex environmental medium by using nuclear receptor protein, and the core is to convert environmental endocrine disruption effect activity into measurable signal output (fluorescence), so that rapid screening of new pollutants is realized. According to the method, the efficiency of screening new pollutants is improved, and the method can be applied to rapid screening of effector activity new pollutants combined with PPAR or ER protein in the environment.

The present disclosure relates generally to compounds which bind to the NR1H4 receptor (FXR) and act as agonists of FXR. The disclosure further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and / or conditions through binding of said nuclear receptor by said compounds and to a process for the synthesis of said compounds.

Described herein are methods of characterizing incorporation of an agent into condensates, methods of reducing transcription of an oncogene associated with a condensate, and methods of using a peptide to inhibit binding of a nuclear receptor and a co-factor in a condensate.

The invention discloses a preparation method and application of renal progenitor cells. The method specifically comprises the following steps: inducing pluripotent stem cells to be differentiated into an intermediate mesoderm cell stage through a GSK-3alpha / beta inhibitor, and inducing cells in the intermediate mesoderm cell stage to be differentiated into a cap-like mesenchymal stage by using a nuclear receptor agonist containing FGF-2 and RAR / RXR, so as to obtain the renal progenitor cells with obvious specific characteristics and potentials of the cap-like mesenchymal. According to the method, the high-purity and high-quality renal progenitor cells can be obtained without separation and purification, the purity can reach 99.9%, and the obtained renal progenitor cells have the differentiation potential of kidney-like organs, basically have no PSCs residues, have the differentiation potential of kidney-like organs and are suitable for clinical cell therapy; and the operation is simple, stable and controllable, and safe, effective, high-purity and homogeneous renal progenitor cells can be prepared on a large scale.

The invention discloses a human zinc finger-truncated nucleus receptor fused small molecule response type gene regulation system and application thereof, and relates to the technical field of gene engineering. The gene regulation and control system contains transcriptional regulation and control protein, and the transcriptional regulation and control protein is formed by fusing a human zinc finger DNA binding module and a truncated nuclear receptor; the human zinc finger DNA binding module can specifically recognize and bind a target DNA regulatory sequence, and the truncated nuclear receptor is combined with a ligand to serve as a transcriptional regulatory module to realize controllable expression of a target gene; the human zinc finger DNA binding module is a human or humanized zinc finger array; according to the truncated nuclear receptor, an inherent DNA binding domain and an N-terminal transcriptional activation region are removed, and a hinge region and a ligand binding region are mainly reserved. The gene regulation system disclosed by the invention has the characteristics of humanization, compact structure, capability of being regulated by small molecules and the like, and in some embodiments, in-vivo or in-vitro controllable expression of a target gene can be realized.

Provided here are nuclear receptor 4A agonists and methods of use for treatment of an infectious disease or an inflammation-related disease. These agonists include 3-(adamantan-1-yl)-1-(2-hydroxy-2-phenylpropyl)urea (available at Life Chemicals as F6279-0659), N-(3-acetylphenyl)-5,6,7,8-tetrahydronaphthalene-2-carboxamide (available at Life Chemicals as F0537-0485), N-[(1-hydroxy-2,3-dihydro-1H-inden-1-yl)methyl]naphthalene-1-carboxamide (available at Life Chemicals as F5857-5371), 3,4-difluoro-N-[(2-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]benzamide (available at Life Chemicals as F6414-1064), N-(3-hydroxy-3-phenylpropyl)naphthalene-1-carboxamide (available at Life Chemicals as F5857-6887), N-(2-hydroxy-3-phenylpropyl)naphthalene-1-carboxamide (available at Life Chemicals as F6200-1091) or a pharmaceutically acceptable salt thereof. These agonists include one or more of F5964-0242, F5964-0253, F1065-0517, F0020-1803, F5857-5401, F0915-2916, F0307-0288, F3350-0754, F6172-0216, F3367-0092, F6172-0224, F5857-2441, F5857-6404, and F5857-5470 (available at Life Chemicals) or a pharmaceutically acceptable salt or derivative thereof.

The present application belongs to the technical field of breast milk biological monitoring, and particularly relates to a method for detecting chemical contaminants in breast milk based on PPAR gamma nuclear receptor affinity selection mass spectrometry, which is used for non-target identification of chemical contaminants in human breast milk, and further evaluates potential PPAR gamma ligands through molecular docking and surface plasmon resonance (SPR). The above detection method links chemical detection directly with receptor-mediated activity, promotes breast milk biological monitoring, makes up for the key knowledge gap of evaluating lactation exposure risk, and provides a basis for discovery and identification of novel contaminants in human breast milk biological monitoring.

This disclosure relates to a method for establishing a HepaRG-based differentiated liver 3D microsphere model and its applications. Specifically, this disclosure provides a chemically defined differentiation medium formulation that does not require DMSO and contains hepatocyte growth factor, dexamethasone, and hepatoprotectin M. Using this medium, HepaRG cells can be efficiently induced to form compact, long-lived 3D microspheres in ultra-low adsorption 96-well plates or in conjunction with high-throughput 3D printing technology. After differentiation and maturation, the model can stably express hepatocyte markers, key drug-metabolizing enzymes, and nuclear receptors at high levels. The liver 3D microsphere model established by this disclosure can effectively simulate hepatocyte function in vivo and is suitable for high-throughput drug hepatotoxicity screening. The results show a high degree of consistency with clinical hepatotoxicity data, and it has important application value in the field of drug safety evaluation.

Disclosed herein are triterpenoid compounds, for example, a compound of Formula (I), and pharmaceutical compositions thereof. Also disclosed herein are methods of their use for treat.

The present invention relates to a modified immune cell for use in the treatment of a solid tumor in a subject wherein the modified immune cell comprises one or more exogenous nucleic acid molecules encoding a transgenic construct targeting an antigen expressed in a cancer cell of said solid tumor, in said immune cell, nuclear receptor subfamily group 2 F member 6 (NR2F6) activity is suppressed (as compared to a control immune cell), and binding of the immune cell to an antigen is associated with death of the cancer cell expressing the antigen, and inducing a secondary immune response against a cancer cell of a solid tumor in a subject, the secondary immune response is non-specific (epitope diffusion) for the antigen targeted to the transgenic construct. The present invention also relates to a modified immune cell comprising one or more exogenous nucleic acid molecules encoding a transgenic construct targeting an antigen expressed in a cancer cell of a solid tumor in which NR2F6 activity and Casite B line lymphoma oncogene-b (CBLB) activity are inhibited (as compared to a control immune cell). The invention also relates to pharmaceutical compositions comprising a modified immune cell suitable for the treatment of solid tumors, additionally comprising a pharmaceutically acceptable carrier, and to in vitro methods for enhancing the cytolytic activity of the modified immune cell.

Modulators of Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1) are described as well as their use as therapeutic agents for disease, disorders, or symptoms thereof, including those where modulation of NR4A1 is implicated. Such disease and disorders include cancer.

The invention discloses an ostrinia furnacalis nuclear receptor HR39 gene, an RNA interference fragment, dsRNA and application thereof, and relates to the field of agricultural pest control. The full-length cDNA sequence of the HR39 gene is as shown in SED ID NO: 1, the amino acid sequence of the coded protein is as shown in SED ID NO: 2, and the sequence of the RNA interference fragment is as shown in SED ID NO: 3. The full-length cDNA sequence of the HR39 gene is obtained, a dsRNA segment targeting the gene is designed, transcription expression of the HR39 gene is successfully interfered, and results show that ovary development of female individuals interfering the HR39 is remarkably inhibited, the egg laying amount and the egg hatching rate are remarkably reduced, and the reproductive capacity of the female individuals is remarkably inhibited. The HR39 gene provided by the invention provides a molecular target for designing a specific and efficient nucleic acid pesticide to inhibit reproduction of pests, and has a good application prospect in green prevention and control of ostrinia furnacalis.

The present application provides the use of aromatic nitroethylenes, in particular, the present application provides the use of a compound represented by formula (I), a stereoisomer or a pharmaceutically acceptable salt thereof for preparing a medicament for modulating the dimer activity of nuclear receptor RXR or treating neurodegenerative diseases.

The invention discloses a totally-enclosed avian influenza H5, H7, H9 and universal virus quadruple detection kit. The kit comprises primers and probes of a universal avian influenza virus M gene, an H5 subtype avian influenza virus HA gene, an H7 subtype avian influenza virus HA gene, an H9 subtype avian influenza virus HA gene and a reference gene LconR. According to the invention, the ligand-dependent nuclear receptor corepressor protein is introduced as a reference gene, and the gene widely exists in mammals and birds and is very suitable for detection of multi-species infection epidemic diseases such as avian influenza. The internal reference can participate in nucleic acid extraction and amplification processes, strictly controls the quality of each detection step, fundamentally avoids false negative results, and significantly improves the reliability of detection results. The internal reference also expands the species application range of the detection method, so that avian influenza detection is not limited to poultry any more, and the method can be widely applied to all mammals possibly infected with avian influenza.

The embodiment of the invention discloses a kinetic analysis method for motion-induced nuclear receptor lactylation. The kinetic analysis method comprises the following steps: acquiring original lactylation related data of a nuclear receptor in a motion process of a motion object on motion equipment; pre-processing the original lactylation related data to obtain pre-processed lactylation related data; based on the change characteristics of the pre-processed lactylation related data, screening out a target model from a plurality of models, and performing parameter optimization; and based on the target model after parameter optimization, analyzing the pre-processed lactylation related data to obtain a whole time sequence lactylation level predicted value of the nuclear receptor.

The embodiments of the present disclosure relate to decreasing the bioavailability of one or more target biomolecules by providing a composition that comprises a recombinant plasmid (RP) and one or more sequences of micro-interfering ribonucleic acid (miRNA). When the RP interacts with a target cell, it causes the target cell to upregulate production of the miRNA, which then decreases the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is a nuclear receptor. In some embodiments of the present disclosure, the nuclear receptor is the androgen receptor.

The invention discloses a technology for inducing mitochondrial membrane damage and an autophagy degradation mechanism based on Raptinal. The technology is used for reducing the content of residual mutation mtDNA carried in the mitochondrial replacement process. According to the method, before nuclear transfer (PNT), a nuclear donor embryo containing mutated mtDNA is placed in a Raptinal operating solution for short-time incubation, so that a mutated mitochondrial membrane is depolarized and damaged, and then the mutated mitochondrial membrane is selectively cleared through the mitochondrial autophagy effect of a nuclear receptor embryo, so that the co-transfer of the mutated mtDNA is remarkably reduced. And cell apoptosis is avoided by adding a pan-caspase inhibitor, so that the balance between membrane injury and embryo survival is realized. C57BL / 6J and BALB / c mice are taken as models, allele-specific PCR (polymerase chain reaction) is used for detecting mtDNA residues of reconstructed embryos, and results show that the detection rate of mutated mtDNA can be reduced from 100% to 30% and the carrying rate of the mutated mtDNA is reduced by more than 70% through Raptinal treatment. The method is easy and convenient to operate, safe, reliable and suitable for the mammalian mitochondrial replacement process, and an efficient new scheme is provided for preventing maternal mitochondrial genetic diseases.

The disclosure relates to an indolo[2′,3′:3,4]pyrido[2,1-b]quinazoline compound represented by general formula (I) and use thereof in the manufacture of (1) a medicament for treating a cardiovascular and cerebrovascular disease, (2) a formulation for increasing expression of AMPK, ABCA1 and SR-BI, (3) a formulation for activating nuclear receptors (NRs), and inhibiting activity of NLRP3, IL-1β, NF-κB and MAPKs, (4) a formulation for promoting cellular cholesterol efflux; or (5) a medicament for anti-inflammation.

Disclosed in the present invention are a method for preparing renal progenitor cells and use thereof. The method specifically comprises: inducing differentiation of pluripotent stem cells into an intermediate mesodermal cell stage by means of a GSK-3α / β inhibitor, and then inducing differentiation of cells in the intermediate mesodermal cell stage into a cap mesenchyme stage by using a combination of FGF-2 and an RAR / RXR nuclear receptor agonist, so as to obtain renal progenitor cells having distinct characteristics and potential specific to the cap mesenchyme. According to the method, high-purity and high-quality renal progenitor cells can be obtained without the need for sorting and purification, and the purity can reach 99.9%; the obtained renal progenitor cells have the differentiation potential of kidney-like organs, are basically free of residual PSCs, have the differentiation potential of kidney-like organs, and thus are suitable for clinical cell therapy. Moreover, the method features simple, stable, and controllable operations, facilitating the large-scale preparation of safe, effective, high-purity, and homogeneous renal progenitor cells.

The invention belongs to the technical field of rapid screening and toxicity evaluation of new pollutants, and discloses a PPAR gamma active substance screening method based on PPAR gamma / RXR alpha heterodimerization. The method is used for detecting the PPAR gamma agonistic / antagonistic activity of chemicals. Aiming at the problems of incomplete biological process simulation, low sensitivity and the like existing in the conventional common reporter gene screening method, the invention constructs a novel screening method: firstly, introducing a chaperone nuclear receptor RXR alpha, and constructing a screening method based on PPAR gamma / RXR alpha heterodimerization so as to more accurately simulate an in-vivo regulation mechanism; and secondly, a co-activation factor NCOA6 (PRIP) is innovatively introduced, the transfection quality is determined to be 50-200ng, and the signal response intensity of the reporter gene is effectively enhanced. Through the work, the lowest effect concentration (LOEC) of the PPAR gamma active substance screening method on the PPAR gamma positive substance rosiglitazone (ROSI) is reduced from 1 mu M to 10 nM, the EC50 value is reduced to 213.4 nM, and the sensitivities are improved by 2.7 times and 100 times respectively. The method is easy and convenient to operate and suitable for efficient and accurate detection of low-concentration PPAR gamma active substances in the environment.

The application discloses a use of a compound shown in formula (I), formula (II) or formula (III) or a tautomer, a stereoisomer, a solvate or a pharmaceutically acceptable salt thereof in preparation of a drug for preventing and / or treating a disease related to a nuclear receptor Nur77 (nerve growth factor-induced gene B, NGFI-B). The compound shown in formula (I), formula (II) or formula (III) can be combined with Nur77, effectively activate Nur77 activity, and can effectively treat and / or prevent a disease related to Nur77.

The present application relates to the technical field of biological monitoring, in particular to a fluorescence sensor for detecting endocrine disrupting activity in sewage and application. The present application creatively designs a Y-shaped polypeptide containing an anchoring region, a hinge region and an anti-fouling region as a structural framework, and performs directional modification at the ends of the main chain and the branch chain to prepare a multifunctional ligand-polypeptide-dye conjugate; a covalent coupling method is used to construct a high-response-efficiency, strong-anti-pollution-characteristic and stable-regeneration optical biosensor chip, i.e. a ligand-polypeptide-dye conjugate functionalized biosensor chip, then a quantum dot-nuclear receptor fluorescence probe with high sensitivity and adjustable emission spectrum is prepared, a ratio fluorescence biosensing principle based on fluorescence resonance energy transfer is proposed, and rapid quantitative detection of endocrine disruptors in sewage is realized, so that the present application has broad-spectrum specific recognition ability for certain endocrine disruptors.

Methods of treating endometriosis through modulation of Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1) activity including administration of an NR4A1 ligand to an individual in need thereof are described. In an embodiment, the compounds include methylene substituted diindolylmethanes.