66 results about "Nuclear receptor" patented technology

The invention belongs to the technical field of medicinal chemistry, and discloses a preparation method and application of a benzofuran [2, 3-b] pyridine derivative of a targeted nuclear receptor co-activator 4 (NCOA4). The derivative has a structural general formula as shown in the following formula (I), wherein R1, R2 and R3 substituent groups can be combined at will. The compounds are combined with NCOA4 to interfere the cell iron autophagy process and effectively inhibit the ferroptosis of various cells induced by RSL3 or Erastin. Particularly, the binding affinity of the compound 4k and NCOA4 is optimal (Kd is equal to 0.78 mu M), and the compound 4k has remarkable ferroptosis inhibition activity and can be used for research and development of medicines for ferroptosis-related diseases. # imgabs0 #

The present invention provides a pharmaceutical composition for preventing or treating ophthalmic diseases, comprising a nuclear receptor subfamily 2 group F member 1 (NR2F1) inhibitor. The NR2F1 inhibitor of the present invention rejuvenates retinal cells by inhibiting the expression of the NR2F1 gene or the activity of the NR2F1 protein, and thus has the effects of reducing cellular senescence of retinal pigment epithelial cells and restoring visual function.

The application discloses application of NCOA7 circular RNA nanoliposome in preparation of a drug for treating premature ovarian failure or ovarian reserve function decline, and belongs to the technical field of biological medicine.The present application proves that nuclear receptor coactivator 7 (NCOA7) can relieve ovarian aging and significantly improve the ovarian function and fertility of DOR patients.The present application finds that NCOA7 circular RNA nanoliposome treatment can significantly improve the NCOA7 protein expression level of DOR female ovarian granulosa cells, improve the aging phenotype and growth rate of the DOR female ovarian granulosa cells, and has no significant influence on the biological characteristics of the ovarian granulosa cells, thereby providing a new scheme for rescuing the ovarian function and improving the fertility of DOR women.

Disclosed herein are compounds which inhibit nuclear receptor-binding SET domain proteins (NSD's), pharmaceutical formulations, and methods of treatment of NSD-mediated diseases, such as certain cancers.

The invention relates to the technical field of biological medicine, in particular to a nuclear receptor truncated variant and application thereof. 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 AR truncated variant can induce transcriptional activation of a downstream signal channel under the condition of deletion of AR-NTD, and a brand new mechanism analysis idea and a treatment target are provided for solving the problem that AR-negative prostate cancer patients are difficult to treat.

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 belongs to the technical field of gene engineering, and particularly relates to application of nuclear receptor LXRs in regulating and controlling the anti-cancer activity of NK cells. The invention provides an application of nuclear receptor LXRs in preparation of a biomarker for detecting the antitumor activity of NK cells. The LXRs comprise LXRbeta and / or LXRalpha; and the LXR beta is expressed in an SLC9B2 signal channel. The invention discloses the effect of the nuclear receptor LXRs in regulating and controlling the anti-cancer activity of the NK cells for the first time.

The invention relates to the technical field of biology, in particular to a lung adenocarcinoma diagnosis marker based on m6A methylation modified circular RNA and application of the lung adenocarcinoma diagnosis marker. The invention discloses a circular RNA (Ribonucleic Acid) hsacirc0079039 combined with m6A recognition protein HNRNPC (Hepatoxin Nuclear Receptor Protein) and application of the circular RNA hsacirc0079039 in methylation modification of the circular RNA m6A. The hsacirc0079039 subjected to methylation modification of the m6A can be used as a biomarker for diagnosing lung adenocarcinoma. The invention has important value for screening and early diagnosis of lung adenocarcinoma.

Provided are methods for treating cancers and / or tumors in subjects. In some embodiments, the methods include administering to a subject an effective amount of a ceramide nanoliposome (CNL), wherein the CNL has a lipid bilayer that includes one or more C2-C24 ceramides and encapsulates one or more anti-cancer and / or anti-tumor agents. Also provided are methods for treating cancers and / or tumors associated with receptor tyrosine kinase or nuclear receptor activities, methods for treating Prostate Cancer, methods for inhibiting growth of EGFR-dependent cancers and / or tumors, methods for inhibiting growth of androgen receptor negative cells, method for reducing or eliminating androgen receptor negative cells from subject, CNLs that encapsulate one or more anti-cancer and / or anti-tumor agents, wherein the CNLs include a lipid bilayer that has one or more C2-C24 ceramides, and pharmaceutical compositions that include the disclosed CNLs.

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.

The present invention relates, inter alia, to a method of treating retinal disease using a splicing modulator, such as an antisense oligonucleotide, capable of inducing natural splicing of exon 6 of mutant nuclear receptor subfamily group 2 E member 3 (NR2E3) pre-mRNA. The invention also provides a composition containing the splicing modifier and application of the composition.

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 invention is directed to, inter alia, a method for treating retinal disease using a splicing modulator, such as an antisense oligonucleotide, capable of inducing the native splicing of exon 6 of a mutant nuclear receptor subfamily, 2 group, E member 3 (NR2E3) pre-mRNA. Also provided is a composition comprising the splicing modulator, and use of same.

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 invention discloses application of cinnamyl aldehyde, and cinnamyl aldehyde can regulate synthesis and secretion of androgen testosterone and can be applied to related products for regulating synthesis and secretion of androgen testosterone. In addition, tests prove that cinnamyl aldehyde increases synthesis and secretion of testicular interstitial cell androgen by improving activity of a steroid hormone synthesis nuclear receptor promoter and up-regulating expression of steroid hormone synthetase.

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.

The current invention relates to nuclear receptor-binding SET domain-containing 2 (NSD2)-targeted protein degradation reagents and pharmaceutical compositions thereof and their utility as anti-cancer agents.

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.

Provided herein are compounds comprising a nuclear payload, such as a topoisomerase inhibitor, a topoisomerase toxic agent, or an analog thereof, and a nuclear receptor targeting epitope.

The application discloses a specific alternative splicing transcript ARRB1 of B-type inhibin 1 Δexon13 , a specific alternative splicing transcript NCOR2 of nuclear receptor auxiliary inhibin 2 Δexon21 . The application also discloses use of a reagent for detecting the specific alternative splicing transcript ARRB1 of B-type inhibin 1 Δexon13 in preparation of a kit for detecting glioma. The application also discloses use of a reagent for detecting the specific alternative splicing transcript NCOR2 of nuclear receptor auxiliary inhibin 2 Δexon21 in preparation of a kit for detecting glioma. The application also discloses use of a reagent for detecting the specific alternative splicing transcript ARRB1 of B-type inhibin 1 Δexon13 in preparation of a kit for detecting breast cancer. The application proves that ARRB1 Δexon13 and NCOR2 Δexon21 have high specific expression in primary and recurrent glioma, and can be used as one of means for pathological diagnosis or prognosis analysis of glioma.

The invention discloses application of nuclear receptor binding protein 2 in treatment of postoperative restenosis neointimal hyperplasia. The overexpressed nuclear receptor binding protein 2 can inhibit phenotypic transformation of vascular smooth muscle cells caused by platelet-derived growth factors (PDGF-BB) and enhancement of proliferation and migration capabilities. In addition, mouse carotid artery neointimal hyperplasia caused by carotid artery guide wire injury can be effectively improved through specific overexpression of the nuclear receptor binding protein 2 through smooth muscle cells, and it is prompted that the nuclear receptor binding protein 2 has a treatment effect and can serve as a marker to be applied to screening of drugs for treating postoperative restenosis neointimal hyperplasia.

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.

To provide methods of characterizing and utilizing agent-condensate interactions.SOLUTION: Described herein are methods of characterizing agent incorporation into condensates, methods of reducing transcription of oncogenes associated with condensates, and methods of using peptides to inhibit nuclear receptor and cofactor binding in condensates. Herein it is shown that transcriptional condensates are implicated in driving oncogenesis and provide a framework for new entry points in cancer therapeutics.SELECTED DRAWING: Figure 22

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.

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.