38 results about "Thyrotropin receptor" patented technology

The present invention discloses a compound represented by the following Formula (I) and a pharmaceutically acceptable salt thereof. The compound improves the THRα selectivity while maintaining good THRβ agonistic activity, thereby improving properties of the finished drug.

To provide a pharmaceutical composition comprising a novel compound which has a thyroid-stimulating hormone receptor antagonist activity and is useful for the treatment of thyroid-related diseases.SOLUTION: There is provided a pharmaceutical composition comprising a 3,4-dihydroquinolin-2(1H)-one compound represented by a formula (I) or a pharmacologically acceptable salt thereof. A pharmaceutical composition comprising the compound or the pharmacologically acceptable salt thereof has an antagonist activity against thyroid-stimulating hormone receptors and is useful as a therapeutic agent or the like for thyroid-related diseases (for example, hyperthyroidism, Graves' disease, thyroid eye disease and thyroid cancer).SELECTED DRAWING: None

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

The present disclosure provides lysosomal targeting bifunctional molecules that target disease causing anti-TSHR autoantibodies for degradation. The lysosomal targeting bifunctional molecules include a ligand moiety that specifically binds to an asialoglycoprotein receptor (ASGPR), and which is linked via a carrier protein to a thyroid stimulating hormone receptor (TSHR) polypeptide that specifically binds target anti-TSHR autoantibodies.

The invention discloses a group of blocking monoclonal antibodies of an SH1 homologous cluster fully human thyrotropin receptor (TSHR) (a TSH receptor, TSHR) as well as a preparation method and application of the blocking monoclonal antibodies of the SH1 homologous cluster fully human thyrotropin receptor (TSHR). The method comprises the following steps: sorting plasma cells and memory single B cells for specifically recognizing TSHR in peripheral blood of a patient with high TSH receptor blocking antibody (TBAb) titer by using flow cytometry, cloning antibody light and heavy chains in vitro and performing recombinant expression, and performing antibody property screening verification by using hTSHR-CHO cells. The blocking monoclonal antibody specifically targeting the human TSHR is obtained. The fully human TSH receptor blocking monoclonal antibody disclosed by the invention can be specifically combined with TSHR, and can effectively block signal transduction after the TSH is combined with the receptor; the synthesis and secretion of thyroid hormone are inhibited; expression and fibrosis of effector cell orbital fibroblasts TSHR for inhibiting thyroid-related eye diseases are remarkably relieved, and wide application prospects are achieved in treatment of Graves' diseases and diseases such as thyroid eye diseases caused by hyperthyroidism.

Disclosed are compounds that are thyroid stimulating hormone receptor antagonists, and methods useful for preventing or treating a thyroid disease.

Provided herein are antigen binding proteins that bind to thyroid stimulating hormone receptor (TSHR) and methods of using the same.

The invention relates to a pair of anti-TSH receptor (TSHR) autoantibody-binding fusion proteins consisting of a capture fusion protein and a detection fusion protein, and a method for detecting autoantibodies to the thyroid stimulating hormone receptor (TSHR) in a biological fluid sample, which employs said fusion proteins pair. More specifically, the capture and detection fusion proteins of the pair of the invention comprise an extracellular domain of a human TSHR and a monomeric non-human immunoglobulin Fc domain, or fragment thereof, or a bacterial maltose binding protein (MBP). Also disclosed is a kit for carrying out the method of the invention. In a preferred embodiment, the method of the invention is a sandwich immunoassay.

The invention relates to the technical field of biology, in particular to an anti-thyroid stimulating hormone receptor monoclonal antibody 7C3 and application. The invention discloses a monoclonal antibody 7C3 for resisting a thyroid stimulating hormone receptor. The sequence of the monoclonal antibody 7C3 comprises a heavy chain variable region as shown in SEQ ID NO.8 and a light chain variable region as shown in SEQ ID NO.17; the monoclonal antibody 7C3 can be combined with natural wild type TSHR, has thyroid irritating activity, can be competitively inhibited by TRAb in serum of a GD patient to be combined with TS HR and the like, can be used for preparing specific therapeutic drugs for resisting irritating TRAb or developing in-vitro diagnostic kits, provides a theoretical basis and a powerful tool for clinical TRAb type detection, and has a wide application prospect. And the TRAb antibody can be used for developing a specific therapeutic drug aiming at the irritant TRAb antibody.

The invention belongs to the technical field of biological medicines, and particularly relates to a drug-loaded vesicle for treating thyroid cancer as well as a preparation method and application of the drug-loaded vesicle. The drug-loaded vesicle comprises a vesicle, wherein a cavity of the vesicle is loaded with radioactive iodine; the membrane surface of the vesicle is modified with: a) a first single-chain antibody fragment capable of specifically binding to thyroglobulin; according to the present invention, after the intravenous injection, the drug-loaded vesicle can be enriched in the thyroid cancer lesion area of the RAIR-DTC patient, such that the cancer cell proliferation is inhibited while the radioactive iodine is continuously released so as to provide the long-term treatment effect;

To provide a new compound having thyroid stimulating hormone receptor antagonist activity and useful for treating thyroid-related diseases.SOLUTION: The present invention relates to a bicyclo [1.1.1] pentane compound represented by the following formula (I) or a pharmacologically acceptable salt thereof. Since the compound of the present invention or a pharmaceutically acceptable salt thereof has an antagonist activity against a thyroid stimulating hormone receptor, it is useful as a therapeutic agent for thyroid-related diseases (e.g., hyperthyroidism, Graves' disease, thyroid ophthalmopathy and thyroid cancer) and the like.SELECTED DRAWING: None

The present invention relates to the field of molecular biology, and more particularly to nucleic acid aptamers, derivatives, and applications thereof for detecting TSHR protein. The present invention provides a nucleic acid aptamer for detecting TSHR protein, the nucleotide sequence of which is shown in SEQ NO. 1. The present invention provides a DNA aptamer YC6 with high affinity for TSHR protein, which has been validated at the molecular, cellular, and tissue levels. The present invention discovers that the DNA aptamer YC6 has the ability to recognize and target cells expressing thyrotropin receptors, providing new insights into the diagnosis and treatment of thyroid diseases and thyroid-related eye diseases.

The invention discloses a group of blocking monoclonal antibodies of an SH23 homologous cluster fully human thyrotropin receptor (TSHR) (a TSH receptor, TSHR), a preparation method of the blocking monoclonal antibodies, and an application of the blocking monoclonal antibodies of the SH23 homologous cluster fully human thyrotropin receptor (TSHR), the SH23 homologous cluster fully human thyrotropin receptor (TSHR) and the preparation method of the blocking monoclonal antibodies. The method comprises the following steps: sorting plasma cells and memory single B cells for specifically recognizing TSHR in peripheral blood of a patient with high TSH-blocking antibody (TBAb) titer by using flow cytometry, cloning antibody light and heavy chains in vitro and performing recombinant expression, and performing antibody property screening verification by using hTSHR-CHO cells, so as to obtain the TSHR-TBAb-TSHR-TBAb. The blocking monoclonal antibody specifically targeting the human TSHR is obtained. The fully human TSH receptor blocking monoclonal antibody disclosed by the invention can be specifically combined with TSHR, and can effectively block signal transduction after the TSH is combined with the receptor; the compound disclosed by the invention has good inhibitory activity in vitro and in vivo experiments, and has a wide application prospect in the aspect of treating Graves' diseases (Graves' disease, GD) and diseases caused by hyperthyroidism, such as thyroid eye diseases (thyroid eye disease, TED) and the like.

Disclosed are compounds that are thyroid stimulating hormone receptor antagonists, and methods useful for preventing or treating a thyroid disease.

The present invention provides a nucleic acid aptamer targeting TSHR protein, a nucleic acid derivative and its application, and belongs to the field of molecular biology technology. The nucleic acid aptamer targeting TSHR protein in the present invention comprises a nucleotide sequence as shown in SEQ ID NO.1, and one or more modifications including radioactive labeling, therapeutic drug connection, fluorescent labeling or biotin labeling are performed on both ends or one end of the nucleic acid aptamer targeting TSHR protein to obtain a nucleic acid aptamer targeting TSHR protein and its derivatives. The nucleic acid aptamer and its derivatives in the present invention can identify and target cells expressing thyrotropin receptors, have high affinity, strong stability, low cost, and have the advantages of in vitro and in vivo imaging labeling functions, providing new molecular tools for the diagnosis and treatment of thyroid diseases and thyroid-related eye diseases.

Described herein are compounds that are thyroid stimulating hormone receptor (TSHR) antagonists, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of TSHR activity.

The invention relates to a pair of anti-TSH receptor (TSHR) autoantibody-binding fusion proteins consisting of a capture fusion protein and a detection fusion protein, and a method for detecting autoantibodies to the thyroid stimulating hormone receptor (TSHR) in a biological fluid sample, which employs said fusion proteins pair. More specifically, the capture and detection fusion proteins of the pair of the invention comprise an extracellular domain of a human TSHR and a monomeric non-human immunoglobulin Fc domain, or fragment thereof, or a bacterial maltose binding protein (MBP). Also disclosed is a kit for carrying out the method of the invention. In a preferred embodiment, the method of the invention is a sandwich immunoassay.

Provided are a group of fully human thyrotropin receptor (TSHR) (TSH receptor, TSHR) blocking monoclonal antibodies belonging to a SH1 homocluster, a preparation method therefor, and a use thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and individual memory B cells, which specifically recognize TSHR, from peripheral blood of a patient having a high TSH receptor blocking antibody (TBAb) titer, cloning antibody light and heavy chains in vitro, followed by recombinant expression, and performing antibody characteristic screening and verification by using hTSHR-CHO cells, thereby obtaining blocking monoclonal antibodies that specifically target human TSHR. The fully human TSH receptor blocking monoclonal antibodies can specifically bind to TSHR, thereby enabling effective blockage of signal transduction after TSH binds to the receptor, inhibiting the synthesis and secretion of thyroid hormones, and significantly reducing and suppressing the expression of TSHR and fibrosis in orbital fibroblasts, the effector cells in thyroid-related eye diseases. The present invention has broad application prospects in the treatment of Graves' diseases and diseases caused by hyperthyroidism, such as thyroid eye diseases.

This invention provides a recombinant thyroid-stimulating hormone receptor (TSHR) protein, its preparation method, and its applications. The recombinant TSHR protein comprises an extracellular TSHR protein segment and an intracellular TSHR protein segment, with the C-terminus of the extracellular TSHR protein segment linked to the N-terminus of the intracellular TSHR protein segment. The protein achieves extracellular soluble expression, high purity, high activity, and good stability.

This invention relates to the field of biotechnology, specifically to an anti-thyroid-stimulating hormone receptor monoclonal antibody 22B1 and its applications. The invention discloses an anti-thyroid-stimulating hormone receptor monoclonal antibody 22B1, the sequence of which includes the heavy chain variable region shown in SEQ ID NO. 8 and the light chain variable region shown in SEQ ID NO. 17. The monoclonal antibody 22B1 exhibits high affinity for TSHR289 protein, can bind to natural wild-type TSHR, possesses thyroid-stimulating activity, and can be competitively inhibited by TRAb in the serum of GD patients, thus exhibiting strong biological activity. It can be used in the preparation of specific therapeutic drugs against stimulating TRAb or in the development of in vitro diagnostic kits, providing a theoretical basis and powerful tool for the clinical detection of TRAb types, and can also be used to develop specific therapeutic drugs against stimulating TRAb antibodies.

The present invention addresses the problem of providing a novel compound that has an antagonistic activity against thyroid-stimulating hormone receptors and is useful for the treatment of thyroid-related diseases.　The present invention relates to a di-substituted bicyclo[1.1.1]pentane compound represented by formula (I) or a pharmacologically acceptable salt thereof. The compound or the pharmacologically acceptable salt thereof according to the present invention has an antagonistic activity against thyroid-stimulating hormone receptors and is useful as, for example, a therapeutic agent for thyroid-related diseases (e.g., hyperthyroidism, Graves' disease, thyroid eye disease, and thyroid cancer).

A chimeric protein comprising an extracellular domain of human thyroid-stimulating hormone receptor (TSHR), said domain lacking a C-terminal segment comprising at least the segment from amino acid residue 301 to 413 of TSHR.

On the basis of a Galpha s-cAMP-PKA signal channel, which plays a normal physiological role in vivo, of thyroid stimulating hormone and the regulation and control effect of the thyroid stimulating hormone on thyroid hormone synthesis, a normal human thyroid follicular epithelial cell line Nthy-ori 3-1 is transformed into a TSHR overexpressed stable cell line for the first time, the expression quantity of TSHR in a cell membrane is obviously increased, and the TSHR expression level is improved; the response sensitivity of the Nthy-ori 3-1 cell to a thyroid stimulating hormone drug is obviously improved; by detecting the synthesis level of cAMP and thyroid hormone before and after the stimulation of the thyroid stimulating hormone, it is verified that the TSHR overexpression Nthy-ori 3-1 cell line established in the research has great superiority for determining the biological activity of the human thyroid stimulating hormone.

The application relates to the field of biotechnology, in particular to an anti-thyrotropin receptor monoclonal antibody 1A4 and application. The application discloses an anti-thyrotropin receptor monoclonal antibody 1A4, the sequence of the monoclonal antibody 1A4 comprises a heavy chain variable region shown in SEQ ID NO. 8 and a light chain variable region shown in SEQ ID NO. 17; the monoclonal antibody 1A4 can have high affinity with TSHR289 protein, can bind to natural wild type TSHR, has thyroid stimulating activity, can be inhibited by TRAb in GD patient serum to compete with the binding to TSHR, and has other biological activities, and can be used for the preparation or development of an in vitro diagnostic kit of specific therapeutic drugs against stimulating TRAb, provides a theoretical basis and a powerful tool for the detection of TRAb types in clinic, and can be used for the development of specific therapeutic drugs against stimulating TRAb antibodies.

The present application relates to the field of bioengineering, and particularly relates to a mutant of thyroid stimulating hormone receptor and a preparation method and application thereof. The present application provides a mutant of thyroid stimulating hormone receptor, wherein one or more of the 321st-360th amino acids of the wild-type amino acid of the thyroid stimulating hormone receptor are deleted. The mutant provided by the present application improves the stability of the protein, improves the temperature sensitivity, and improves the gradient and potency and other functions, and does not change the ability of binding with enzyme-labeled antibodies and autoantibodies.

Provided herein are antigen binding proteins that bind to thyroid stimulating hormone receptor (TSHR) and methods of using the same.

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).

The invention discloses a nucleic acid inhibitor of a targeted thyroid stimulating hormone receptor and application. The nucleic acid inhibitor has high targeting property, and can accurately recognize TSHR and avoid off-target effect; the inhibition effect is strong, and the TSHR function can be obviously blocked under the micro-mole or even nano-mole concentration; as a nucleic acid molecule, the nucleic acid molecule does not cause obvious immune response and is suitable for long-term treatment; good biological stability: after chemical modification, excellent serum stability and tissue penetrating ability are achieved; the compound is suitable for various administration routes, is convenient for clinical transformation, and shows a wide clinical application prospect in treatment of various TSHR-mediated autoimmune and neoplastic diseases such as Graves diseases, thyroid-related eye diseases, TSHR activated mutation-driven thyroid cancer and the like. Especially for moderate and severe TED patients lacking effective specific targeted therapy means at present, the nucleic acid inhibitor is expected to become the first precise therapy for directly intervening the TSHR pathogenic core link.