17 results about "Thyrotropin receptor" patented technology

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

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;

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

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.

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.

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.

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.

The present invention provides multispecific antibodies against insulin like growth factor I receptor (IGF-1R) and thyroid stimulating hormone (TSH) receptor (TSHR), methods for their production, pharmaceutical compositions containing the multispecific antibodies, and uses thereof. More particularly, the presently disclosed invention provides bispecific IGF-lR and TSHR antibodies, and antigen binding fragments thereof.

The present application provides a novel compound having a thyroid stimulating hormone receptor antagonistic activity, which is useful for treating thyroid-related diseases. The present application relates to a nitrogen-containing fused ring compound represented by the following formula (A-I) or a pharmacologically acceptable salt thereof. The compound of the present application or a pharmacologically acceptable salt thereof has an antagonistic activity against a thyroid stimulating hormone receptor, and is thus useful as a therapeutic agent for thyroid-related diseases (e.g., hyperthyroidism, Graves' disease, thyroid eye disease, and thyroid cancer), and the like.

Provided are a group of SH23 homologous cluster fully-human thyrotropin receptor (TSH receptor, TSHR)-blocking monoclonal antibodies, a preparation method therefor and the use thereof. The method comprises the following steps: by means of flow cytometry, sorting plasma cells and memory single B cells that specifically recognize TSHR from the peripheral blood of a patient with a high TSH receptor-blocking antibody (TSH-stimulating blocking antibody, TBAb) titer, performing in-vitro cloning of light and heavy chains of the antibody, performing recombination and expression, and carrying out antibody property screening and verification by using TSHR-CHO cells to obtain a blocking monoclonal antibody that specifically targets human TSHR. The fully-human TSH receptor blocking monoclonal antibodies can specifically bind to TSHR, can effectively block the signal transduction after TSH binds to a receptor, and have good inhibitory activity in in vitro and in vivo experiments, and therefore have broad application prospects in the treatment of diseases, such as Graves' disease (GD) and hyperthyroidism-induced diseases, such as thyroid eye disease (TED).