34 results about "Hormone receptor" patented technology

Provided is a bifunctional compound, or a pharmaceutically acceptable salt, hydrate, solvate, metabolite or prodrug thereof, wherein the bifunctional compound is represented by Formula (I) : ABM-L-CLM (I); wherein: ABM is an androgen receptor binding moiety; -L-is a linking moiety; and CLM is a cereblon E3 ubiquitin ligase binding moiety represented by Formula (II) -1: wherein one end of the -L-is covalently joined to Q3, Q4, Q5 or Q6; and the other end of the -L-is covalently joined to the ABM. Also provided are a pharmaceutical composition comprising the bifunctional compound and a method for treating an androgen receptor related disease or disorder by administering the bifunctional compound.

The present invention provides radiolabeled 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-α]indol-9-yl]pyridin-2(1H)-one derivatives of general formula (I) or salts thereof, as well as precursors of the radioligands of general formulae (II) and (III), processes for their preparation, and intermediates of the processes. The radiolabeled compounds enable visualization and quantification of melanin-concentrating hormone receptor 1 (MCHR1) in various target tissues, including monitoring MCHR1 in such target tissues. The compounds exhibit high binding affinity for MCHR1 and are able to cross the blood-brain barrier, thus facilitating diagnosis of various disease states in human clinical studies.

The present invention is directed to a therapeutic agent for use in the treatment of a disease associated with gain-of-function of androgen receptor (AR) and / or with overexpression of an AR coactivator, such as Kennedy disease or cancer. The therapeutic agent of the invention comprises at least one inhibitor of an androgen receptor (AR) coactivator, selected from protein arginine methyltransferase 6 (PRMT6) inhibitor, lysine specific demethylase 1 (LSD1) inhibitor, or combinations thereof.

Described herein are radiotherapeutics that target tumor cells expressing the follicle-stimulating hormone receptor (FSHR) and their use in the treatment and / or diagnosis of cancer.

The present invention relates to a novel compound for autophagy-mediated targeted degradation of an androgen receptor and medical use thereof. The novel compound according to the present invention is an autophagosome-tethering compound (ATTEC) targeting an androgen receptor, which has not been previously reported, and exhibits excellent binding affinity for the androgen receptor and the autophagy marker LC3, and thus can activate autophagy and ultimately target and degrade the androgen receptor, thereby effectively treating androgen receptor-associated diseases.

This invention discloses a novel class of peptides for targeted cancer therapy and their corresponding drug or fluorescent dye conjugates, belonging to the field of biomedical technology. These peptides are designed based on the optimized structure of natural LHRH-III, enabling them to specifically bind to and efficiently internalize into tumor cells overexpressing luteinizing hormone-releasing hormone receptor (LHRH-R). After fluorescent conjugation, their targeting ability against 4T1 cells is comparable to that of the classic peptide [D-Lys]. 6 The [-LHRH-I] peptide exhibits comparable to or superior performance and significantly improves cellular internalization efficiency. In vivo distribution studies have shown that its liver accumulation is significantly reduced compared to the control group, effectively lowering the risk of hepatotoxicity. Furthermore, by conjugating the targeting peptide with antitumor drugs (such as camptothecin or doxorubicin) via disulfide linkers, the resulting peptide-drug conjugates (PDCs) demonstrate excellent responsive drug release characteristics and good in vitro and in vivo antitumor activity. The peptides and conjugates provided by this invention have potential application value in cancer targeted therapy and diagnosis with high specificity and low toxicity.

The disclosure provides methods for treating estrogen receptor positive (ER+) cancer in a patient who has progressed on an aromatase inhibitor. Of particular interest are ER+ cancers that do not harbor a gain of function missense mutation within the ligand binding domain (LBD) of the Estrogen Receptor 1 (ESR1) gene. The provided methods involve the administration of an effective amount of lasofoxifene, a pharmaceutically acceptable salt, prodrug or functional derivative thereof.

The present invention is in the field of molecular subtyping of tumor samples and therapy guidance. The present invention relates to methods, arrays, prognostic assays, systems and uses thereof for prediction of the response or resistance to and / or benefit from a systemic treatment, in particular adjuvant or neoadjuvant chemotherapy, of a subject suffering from a HR+ and HER2− breast cancer, based on the measurement(s) of expression level(s) of three or more markers in tumor samples of said subject. Equally, the present invention relates to methods, arrays, prognostic assays, systems and uses thereof for prediction of the outcome benefit from a systemic treatment, in particular adjuvant or neoadjuvant chemotherapy, of a subject suffering from a HR+ and HER2− breast cancer, based on the measurement(s) of expression level(s) of three or more markers in tumor samples of said subject.

The present application relates to the technical field of inhalation anesthetic antagonism, and particularly relates to the application of a corticotropin-releasing hormone receptor antagonist in the preparation of an inhalation anesthetic antagonist. The present application first discovers that the corticotropin-releasing hormone receptor of the dorsal raphe nucleus is a key target of the action of an inhalation anesthetic, and that the oculomotor nerve parvocellular nucleus-dorsal raphe nucleus neural loop mediates the effect of an inhalation anesthetic, and that a corticotropin-releasing hormone receptor antagonist can block the excitatory effect of urocortin on the neurons of the dorsal raphe nucleus, thereby weakening the effect of an inhalation anesthetic. The present application first applies a corticotropin-releasing hormone receptor antagonist in the preparation of an inhalation anesthetic antagonist, fills the technical gap in this field, is conducive to the rapid postoperative recovery of patients under general anesthesia, and has a broad application prospect.

This article describes heterobifunctional small molecules, methods of preparation, pharmaceutical compositions and medicines comprising such heterobifunctional small molecules, and methods of using such heterobifunctional small molecules to treat diseases and conditions such as cancer, autoimmune diseases and inflammatory diseases.

A composition comprising an androgen receptor inhibitor. The composition can improve the stability of a drug, slow down an increase in impurities, and be stored at room temperature. As a topical dosage form, the composition has bacteriostatic ability, and no additional bacteriostatic agent needs to be added. The composition can achieve the same efficacy while using a lower dose and a lower administration frequency, and has the advantages of significant safety, efficacy and medication compliance.

Embodiments of the invention are directed to the treatment of subjects with prostate cancer, in particular those with castration resistant prostate cancer, with glucocorticoid receptor antagonists. The prostate cancer may be one that has become resistant to androgen deprivation therapy, for example, by increase in glucocorticoid receptor expression and / or activity.

Breast cancer is a serious type of cancer that affects many women each year, often leading to death. To choose the right treatment for breast cancer, studying biomarkers is crucial, and one way to do this is by using the immunohistochemical technique (IHC). Biomarkers like Estrogen receptor (ER), progesterone receptor (PR), Ki67, and P53 play a crucial role in determining the prognosis, progression, and response to treatment of breast cancer. Specific monoclonal antibodies against these biomarkers were created by immunizing mice with peptides derived from these proteins. These antibodies were then tested for specificity using ELISA and IHC staining on normal and cancerous tissues, confirming their ability to recognize the receptors. Additionally, the antibodies were evaluated for isotype, affinity constant, and their ability to detect natural antigens in flow cytometry and western blot.

This invention relates to the treatment of breast cancer in a subject, and the subject can be either a male or female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed selective estrogen receptor modulator (SERM) (tamoxifen, toremifene, raloxifene), gonadotropin-releasing hormone (GnRH) agonist (goserelin), aromatase inhibitor (AI) (letrozole, anastrozole, exemestane), cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitor (palbociclib (Ibrance), ribociclib (Kisqali), lerociclib, abemaciclib (Vorzenio), trilaciclib, lerociclib), mTOR inhibitor (everolimus), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), alpelisib (Piqray) (an inhibitor of phosphatidylinositol-3-kinase subunit alpha (PI3Kα)), lapatinib, neratinib (Nerlynx), olaparib (Lynparza) (an inhibitor of the enzyme poly ADP ribose polymerase (PARP)), bevacizumab (Avastin), and / or fulvestrant treatments; metastasis in a subject suffering from breast cancer; HER2-positive; treating a subject suffering from ER mutant expressing breast cancer and / or treating breast cancer in a subject, by first determining the 18F-16β-fluoro-5α-dihydrotestosterone (18F-DHT) tumor uptake and identifying said subject as having AR-positive breast cancer based on 18F-DHT tumor uptake, comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound and a cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitor.

The application discloses a novel pyridazine compound and a pharmaceutical composition and application thereof, and particularly relates to a compound, a solvate, a stereoisomer, a tautomer, an isotopic derivative or a pharmaceutically acceptable salt of formula (I0-1) or (I0-2), a pharmaceutical composition containing the compound and an application in preventing and / or treating a thyroid hormone receptor related disease.

The present invention addresses the problem of providing a novel compound that has an antagonistic activity against a thyroid-stimulating hormone receptor and is useful for the treatment of thyroid-related diseases. The present invention relates to an N-substituted piperidone compound represented by the following formula or a pharmaceutically acceptable salt thereof. The compound or the pharmaceutically acceptable salt thereof according to the present invention has an antagonistic activity against a thyroid-stimulating hormone receptor and is useful, for example, as a therapeutic agent for thyroid-related diseases (e.g., hyperthyroidism, Graves' disease, thyroid eye disease, and thyroid cancer).

To induce cancer cell death, cancer cells are selected that express estrogen-receptor β (ERβ) and mutant tumor protein 53 (TP53). An agent that increases ERβ protein expression is administered to the cells to induce cell death. To treat a subject having a cancer that is characterized by cancer cells expressing ERβ and mutant TP53, an agent that increases ERβ protein expression is administered to induce cell death in the cancer cells. To increase estrogen receptor β (ERβ) expression levels in a subject having low ERβ expression levels, tamoxifen is administered to increase ERβ protein levels in the subject. To treat a subject having cancer cells expressing estrogen-receptor β (ERβ) and wildtype tumor protein 53 (TP53), an agent that inhibits ERβ and TP53 binding interaction is administered to induce cell death in the cancer cells of the subject.

The present application provides a kind of estrogen receptor positive breast cancer fluorescent probe by parent nucleus dye nile blue derivative, estrogen receptor (ER) recognition group tamoxifen and alkane chain three parts constitute, the probe has the structure of general formula 1.The probe shows folded conformation in water environment, there is photoinduced electron transfer effect between nile blue derivative and tamoxifen, no obvious fluorescence signal;When the probe recognizes ER protein, the recognition group is combined with the binding site, the conformation of the probe changes into unfolded conformation, and strong fluorescence signal is shown.The excitation wavelength of the probe is about 630 nm, the emission wavelength is about 640-700nm, has stronger tissue penetration ability, lower tissue self-absorption and light scattering, can be targeted to breast cancer cell overexpressed ER protein, and specifically highlights estrogen receptor positive breast cancer.

Heterobifunctional small molecules, methods of making, pharmaceutical compositions and medicaments comprising such heterobifunctional small molecules are described herein, and methods of using such heterobifunctional small molecules in the treatment of diseases and conditions, such as cancer, autoimmune diseases, and inflammatory diseases are described herein.

This disclosure relates to benzo(hetero)cycloalkyl compounds or pharmaceutically acceptable salts thereof for the treatment or prevention of androgen receptor-dependent disorders. Specifically, this disclosure relates to compounds of formula (I), pharmaceutical compositions comprising these compounds, and the use of these compounds in the prevention or treatment of diseases, particularly androgen receptor-dependent disorders. JPEG2026518325000079.jpg41121

This invention discloses a method for preparing a key intermediate of an androgen receptor inhibitor. The method uses (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile or its salt and 5-acetyl-1H-pyrazol-3-carboxylic acid as starting materials, and synthesizes the compound (S)-5-acetyl-N-[1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propyl-2-yl]-1H-pyrazol-3-carboxamide (Formula 1) under the action of a triazine condensing agent. This method has the advantages of simple and safe operation, low cost, and high yield, providing a new industrially feasible method for the synthesis of dallotamine.

The idea of the patent includes a new principle, which is the detection of immune complexes using ELISA technology, which is a new and modern principle that is added to the four principles of ELISA, the new principle (the fifth ELISA) depends on detection of immune complexes, which consist of two different parts of proteins (an antigen - an antigen). This complex can be detected through this new principle, and it was applied to the immune complex (thyroid-stimulating hormone receptors and antibodies formed against it) Hashimoto's patients. It was considered an example of applying this theory, the immune complex was actually detected, its concentration determined, and compared to other techniques. A standard solution specially designed for this purpose was used to prove this theory. In this patent, a new kit is specifically designed to detect these immune complexes. Immune complex, the group is considered successful. In terms of use.

Provided is a bifunctional compound, or a pharmaceutically acceptable salt, hydrate, solvate, metabolite or prodrug thereof, wherein the bifunctional compound is represented by Formula (I) : ABM-L-CLM (I); wherein: ABM is an androgen receptor binding moiety; -L-is a linking moiety; and CLM is a cereblon E3 ubiquitin ligase binding moiety represented by Formula (II) -1: wherein one end of the –L–is covalently joined to Q3, Q4, Q5 or Q6; and the other end of the –L–is covalently joined to the ABM. Also provided are a pharmaceutical composition comprising the bifunctional compound and a method for treating an androgen receptor related disease by administering the bifunctional compound.

The present invention relates to new ligands of the follicle stimulating hormone (FSH) receptor for use in the diagnosis and treatment of neuroblastoma.

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of an Androgen Receptor (AR) gene. The AR RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an AR gene. Pharmaceutical compositions that include one or more AR RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described AR RNAi agents to central nervous system (CNS) tissue and / or skeletal muscle tissue, in vivo, provides for inhibition of AR gene expression and a reduction in AR activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including spinal and bulbar muscular atrophy (SBMA).

The present invention provides a method and composition for reversibly localizing proteins to the outer portion of the cell surface. [Solution] Essentially, the protein must include a hormone receptor such as estrogen receptor alpha or progesterone receptor in addition to the transmembrane domain. The compositions provided herein may include nucleic acids encoding the polypeptide of interest and the ligand-binding domain (LBD) of a nuclear hormone receptor. Medical applications are provided, including controlling the toxicity of CAR T cells.