97 results about "DNA receptors" 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 belongs to the technical field of biological medicines, and particularly relates to application of an FXR agonist combined with a PD1 / PD-L1 monoclonal antibody in preparation of an anti-liver cancer medicine, in particular to application of obeticholic acid (OCA) combined with a Czodiasumab in treatment of liver cancer. The invention also provides an application of the nuclear receptors FXR and PD1 in liver cancer treatment, specifically, the nuclear receptors FXR and PD1 are taken as double targets, and the medicine for treating liver cancer is obtained. An FXR agonist OCA is used for activating FXR, and it is found that activation of FXR can regulate immune infiltration of T cells by promoting polarization of macrophage M1, so that growth of tumors is inhibited. In addition, expression of PD-L1 in liver cancer can be promoted by activating FXR, and a better tumor inhibition effect can be achieved by combining an FXR agonist OCA with a PD1 monoclonal antibody for immunotherapy.

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 invention relates to a method for regulating and controlling selective absorption of cadmium and manganese by plants through dephosphorylation. The STNP-mediated phosphorylation is crucial to the selective uptake of cadmium and manganese of solanaceae NRAMP5 (Nuclear Receptor Amplification Protein 5). Simulation of non-phosphorylated mutation in NRAMP5 reduces the absorption of plants to cadmium without affecting the absorption of plants to manganese.

The invention discloses an acyl phloroglucinol compound with a 6 / 6 / 6 tricyclic skeleton and application of the acyl phloroglucinol compound in preparation of an anti-Alzheimer's disease medicine, and relates to the technical field of medicines. The invention provides a method for preparing acyl phloroglucinol compounds with 6 / 6 / 6 tricyclic skeletons from hypericum plants through separation means such as silica gel column chromatography, ODS column chromatography and high performance liquid chromatography. The acylphloroglucinol compound has a direct binding effect with a nuclear receptor RXR alpha, regulates the expression of ABCA1 protein by targeting RXR alpha up-regulation, plays a role in promoting A beta removal, and can be applied to preparation of anti-Alzheimer's disease drugs taking the nuclear receptor RXR alpha as a target spot.

Provided herein are methods and compositions for disrupting expression of nuclear receptor interacting protein 1 (Nrip1) in adipose cells, and methods of use of such adipose cells for treating, or reducing risk of, a condition associated with an elevated body mass index (BMI).

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.

Provided herein are methods and compositions for disrupting expression of nuclear receptor interacting protein 1 (Nrip1) in adipose cells, and methods of use of such adipose cells for treating, or reducing risk of, a condition associated with an elevated body mass index (BMI).

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.

Compositions and methods are disclosed herein for inducing (up-regulating) the expression of sulfotransferases in the hair follicles, e.g., the scalp. Increasing sulfotransferase is beneficial for metabolizing pro-drugs that require sulfonation to be activated, e.g., minoxidil sulfate is the active metabolite of minoxidil. A method for combining the compositions described herein with topical minoxidil to enhance minoxidil treatment for androgenetic alopecia is described. Additional methods and compositions include the use of retinoid X receptor agonists, retinoic acid receptor agonists, and nuclear receptor agonists in an RXR-NR heterodimer. Additional methods and compositions include the use of a topical solution containing an alkalinizing agent or an alkalinizing agent used with a penetration enhancer for up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and / or keratinocyte cells. In addition, compositions and methods for increasing or decreasing the growth rate of hair follicles is disclosed by altering the intracellular pH. Additionally, methods for preparing a stable liposomal containing solution are described.

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 invention belongs to the technical field of medical chemistry, and discloses an aza aromatic amine protein degradation targeting chimera (PROTAC) compound with the activity of degrading nuclear receptor co-inhibitor 1 (NCoR1) in a targeting manner, and a preparation method and application of the aza aromatic amine protein degradation targeting chimera (PROTAC) compound. The aza aromatic amine compound is prepared through acylation and N-alkylation reaction, and the structure of the compound is shown as a formula I to a formula IV. A Liver X Receptor Response Element-Luciferase reporter gene system (LXRE-Luc luciferase reporter gene system) determination experiment shows that when the compound is 10 [mu] M, the compound has an obvious liver receptor (LXR) regulation effect, and the compound has an obvious liver receptor regulation effect when the compound is 10 [mu] M; western blot experiment research shows that the compound has a remarkable degradation effect on NCoR1, and the compound XH-10 with the highest activity can generate a remarkable NCoR1 degradation effect when the concentration is 5 mu M. The compound is PROTAC with NCoR1 targeted degradation activity, and has the advantages of high activity and simple preparation process. The compound has an important value in the aspect of glycometabolism and ester metabolism regulation medicine development.

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.

To provide methods for treatment of diseases.SOLUTION: The present disclosure relates to formulations, such as tablets, of FXR agonists and therapeutic uses thereof. The disclosure also relates to methods for obtaining such formulations. The present disclosure relates to formulations of compounds that bind to the NR1H4 receptor (FXR) and act as agonists or modulators of FXR. The disclosure further relates to the uses of formulations of such compounds for treatment and / or prophylaxis of diseases and / or conditions through binding of the nuclear receptor by the compounds.SELECTED DRAWING: Figure 2B

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.