26 results about "Thyroid hormone receptor" patented technology

The present disclosure relates generally to compounds and compositions thereof for inhibition of thyroid stimulating hormone receptor (TSHR).

The invention discloses thyroid hormone receptor beta subtype agonist derivatives, and a preparation method and application thereof.

The invention provides a pyridazinone compound, or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, and also provides a method related to preparation and application of the compound, a pharmaceutical composition containing the compound and a treatment method of related metabolic diseases. The compound disclosed by the invention shows an excellent thyroid hormone receptor excitation effect and has a wide application prospect in the field of metabolic disease treatment.

The invention relates to pyridazinone or pyridazine compounds as well as derivatives and pharmaceutical compositions thereof. Specifically, the invention provides a pyridazinone or pyridazine compound as shown in a formula (I) or (Ia) or a stereoisomer, a tautomer, an enantiomer, a diastereoisomer, a resonator, a pharmaceutically acceptable salt, a hydrate, a solvate or a crystal form of the pyridazinone or pyridazine compound. The compound shown in the formula (I) or (Ia) has excellent agonistic effect and pharmacodynamic performance on a thyroid hormone beta receptor.

The present invention provides pyridazinone compounds, their stereoisomers, tautomers, or pharmaceutically acceptable salts, as well as methods related to the preparation and use of these compounds, pharmaceutical compositions containing these compounds, and methods for treating related metabolic diseases. The compounds of the present invention exhibit excellent thyroid hormone receptor activating effects and show promising potential for application in the field of metabolic disease treatment.

Provided is a compound useful as a thyroid hormone receptor β-selective thyroid hormone analog. A compound represented by Formula (1), a salt thereof, or a solvate thereof is provided.

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.

The invention belongs to the field of biological medicine, and particularly relates to an oxazolone compound and a preparation method, a pharmaceutical composition and application thereof. The invention provides a compound as shown in a formula (I) or a stereoisomer, a geometric isomer, a tautomer, a deuterated compound, a nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or prodrugs of the stereoisomer, the geometric isomer, the tautomer, the deuterated compound, the nitrogen oxide, the solvate, the metabolite and the pharmaceutically acceptable salt of the compound as shown in the formula (I), and also provides a preparation method of the compound. The invention also relates to application of the compound in preparation of drugs for thyroid hormone receptor mediated diseases. According to the compound, good THR-beta agonist activity is maintained, selectivity to THR-alpha and druggability of the compound are improved, and certain activity is shown in an in-vitro molecular level experiment.

The invention belongs to the field of biological medicine, and discloses application of a thyroid hormone receptor gene Thrb or Thra inhibitor in preparation of a medicine for treating nerve injury. Researches show that thyroid hormone is not beneficial to recovery of spinal cord after zebra fish is completely transected, and siRNA fragments of Thrb or Thra have a remarkable effect on promoting growth of cortical neurons and can also promote expression of p-S6. Therefore, Thrb and Thra are taken as molecular intervention targets, and an inhibitor is used for inhibiting expression of the molecular intervention targets, so that growth and regeneration of cortical neurons can be promoted, expression of p-S6 is promoted, activation of a PI3K-AKT pathway is promoted, and a new possibility is provided for preparing the medicine for treating nerve injury.

The present invention provides a compound, preferably a thyroid hormone receptor beta, THRbeta, agonist compound, compositions thereof, methods of making and methods of agonizing THRbeta, and methods for treating conditions mediated by THRbeta.

The invention provides application of thyroxine and a thyroxine receptor inhibitor in preparation of a medicine for regulating primordial follicle activation, and belongs to the technical field of biology. It is found that thyroxine can promote primordial follicle activation, the thyroxine receptor inhibitor inhibits primordial follicle activation, and the thyroxine receptor inhibitor can serve as a medicine for adjusting primordial follicle activation of a patient suffering from premature ovarian insufficiency and has a good application prospect.

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 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 invention relates to a substituted aza-uracil compound as shown in a formula (I), and an isotope form, a stereoisomer, a tautomer, a cis-trans-isomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a hydrate, a prodrug and a polymorphic substance of the substituted aza-uracil compound. The compound has a good agonistic effect and high selectivity, so that the compound has a good application prospect in the aspect of preparing medicines for preventing and / or treating THR-beta activity mediated diseases.

The present disclosure relates to the technical field of antibody engineering, and specifically provides a polypeptide fragment thyroid hormone receptor betal (THRB)-CVD20, and a polyclonal antibody prepared using the same and use thereof. The present disclosure provides a polypeptide fragment THRB-CVD20, wherein the polypeptide fragment has an amino acid sequence shown in SEQ ID NO: 1. The present disclosure further provides a preparation method of the polypeptide fragment and a polyclonal antibody prepared using the polypeptide fragment. In the present disclosure, the polyclonal antibody can accurately identify target cells due to high sensitivity and specificity, and can be further used to identify, identify, and screen the THRB.

The present invention provides a recombinant thyroid stimulating hormone receptor protein, a preparation method therefor and an application thereof. The recombinant thyroid stimulating hormone receptor protein comprises a TSHR protein extracellular segment and a TSHR protein intracellular segment. The C-terminus of the TSHR protein extracellular segment is linked to the N-terminus of the TSHR protein intracellular segment. The protein achieves extracellular soluble expression, and is high in purity, high in activity and good in stability.

Provided are a selective thyroid hormone receptor-β agonist, a pharmaceutical composition comprising same, and a use thereof. Specifically provided is a compound represented by formula (I). The compound has excellent efficacy and / or specificity, and can be used for treating metabolism-related diseases.

Provided are a polycyclic thyroid hormone β receptor agonist and the use thereof. Specifically, the present invention relates to a compound as represented by formula (1) or a pharmaceutically acceptable form thereof, a pharmaceutical composition containing same, and a preparation method therefor and the use thereof. The compound or pharmaceutical composition can be used for the preparation of a drug for preventing, treating or alleviating diseases regulated by the thyroid hormone β receptor.

The invention discloses a nucleic acid aptamer capable of recognizing and combining different epitopes of a thyroid stimulating hormone receptor as well as a screening method and application of the nucleic acid aptamer. The invention provides a nucleic acid aptamer capable of identifying and combining a thyroid stimulating hormone receptor, which is a single-chain DNA molecule as shown in SEQ ID No.1, 3, 4 or 5. The invention also provides a complete set of nucleic acid aptamer consisting of the nucleic acid aptamer and a nucleic acid aptamer as shown in SEQ ID No.2 or 6. In addition, the invention also provides a method for screening different epitope aptamers, which comprises the following steps of: occupying corresponding epitopes on a target protein by using the screened aptamers, and then carrying out subsequent screening, so that the screened aptamers bound to target other different epitopes on the target protein. Based on the principle, the invention has important research significance on screening of a certain target protein to obtain nucleic acid aptamers for identifying different sites, development of protein detection reagents and bivalent nucleic acid aptamers for enhancing affinity between the nucleic acid aptamers and targets and the like.

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.

The present invention discloses compounds of formula (I), as thyroid hormone receptor β subtype agonists or modulators for use in methods of treatment of obesity, hyperlipidemia, hypercholesterolemia, diabetes mellitus, nonalcoholic steatohepatitis (NASH), hepatic steatosis, arteriosclerosis, cardiovascular disease, hypothyroidism, overweight, fibrosis, thyroid cancer and alopecia, and in chronic weight management or weight management.

Disclosed in the present invention is a thyroid hormone receptor β (THR-β) agonist. The present invention provides a compound as represented by formula I, or a stereoisomer or pharmaceutically acceptable salt thereof. Compared with VK-2809, the compound provided in the present invention has significantly superior agonistic activity against THR-β than VK-2809, or in terms of in vivo organ / tissue distribution, has a liver / heart distribution ratio or plasma / heart distribution ratio superior to that of VK-2809.

The invention belongs to the field of medicine, and discloses a thyroid hormone beta receptor agonist, a crystal form, a preparation method and application, the compound is a compound with a structural formula shown in a formula (I) or pharmaceutically acceptable salt thereof, Cu-Ka radiation is used, X-ray powder diffraction of the A crystal form of the compound shown in the formula (I) expressed by a 2 theta angle at 6.10 + / -0.20 degrees, 12.08 + / -0.20 degrees, 12.08 + / -0.20 degrees, 12.08 + / -0.20 degrees, 12.08 + / -0.20 degrees, 12.08 + / -0.20 degrees, 12.08 + / -0.20 degrees, 12.08 + / -0.20 degrees and a characteristic peak exists at 16.49 + / -0.20 DEG C. The invention develops a novel 2-pyridone derivative, and the compound has high agonistic activity and selectivity to a thyroid hormone beta receptor, and can be used for treating metabolic diseases, especially diseases related to the thyroid hormone receptor. The invention also researches a series of crystal forms of the compound, and the crystal form A compound has the advantages of good stability, low hygroscopicity and small heat influence. # imgabs0 #

The present invention relates to a polymorph of a compound that can be used as a thyroid hormone β receptor modulator, a preparation method therefor and a use thereof, and a pharmaceutical composition containing the polymorph. The use is a use in the preparation of drugs for treating various thyroid-related diseases.

The present invention relates to a thyroid hormone receptor β subtype agonist derivative, a method for producing the same, and uses thereof.

The present application relates to compounds of formulae (B') and (C) and compositions thereof for inhibition of thyroid stimulating hormone receptor (TSHR) and their use in the treatment of diseases such as Grave's disease.