48 results about "Gnrh receptor" patented technology

The present invention relates to Gonadotropin Releasing Hormone (GnRH, also known as Luteinizing Hormone Releasing Hormone) receptor antagonists.

GnPRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein A, R1, R2, R3a, R3b, R4, R5, R6 R7 and n are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

The present invention relates to Gonadotropin Releasing Hormone (GnRH, also known as Luteinizing Hormone Releasing Hormone) receptor antagonists.

The present invention relates to Gonadotropin Releasing Hormone (GnRH, also known as Luteinizing Hormone Releasing Hormone) receptor antagonists.

The present invention relates to Gonadotropin Releasing Hormone (GnRH, also known as Luteinizing Hormone Releasing Hormone) receptor antagonists.

The invention belongs to the pharmacological field of gene engineering, and provides a group of protein derivatives of human granzyme B by adopting gene engineering technology. The group of protein derivatives of the human granzyme B comprises GrB-G4S-GnRH (GrBLG) and mGrB-C4S-GnRH (mGrBLG) which are targeted fusion proteins formed by connecting human matured granzyme B (GrB) and mutagenic human matured granzyme B (mGrB) with human gonadotropin-releasing hormone (GnRH) through flexible connecting short peptide GlyGlyGlyGlySer (G4S) respectively and which can be combined with human GnRH receptors (GnRHR) on the surfaces of cells through ligand human GnRH. The mGrB eliminates the functions of the combination through a personal 'electrostatic exchange-absorption mode' and the entering into target cells of the prior GrB, and simultaneously reserves the enzymatic activity and the cytocidal function of the GrB. The invention provides experimental evidences for peculiarly targeted-killing GnRHR positive cells and minimizing toxic side effect by the fusion proteins, and shows the use of the group of protein derivatives of the human granzyme B in the targeted therapy on the positive adenocarcinoma of a type of gonadotropin-releasing hormone receptors.

Chicken II and salmon GnRH analog decapeptides resistant to degradation by peptidase incorporating D-arginine, D-leucine, D-tBu-Serine, D-Trp or other active D amino acids at position 6 and ethylamide, aza-Gly-amide or other Gly amide at position 10. The analogs demonstrate preferential binding to male and female reproductive system GnRH receptors. Biopotency is greater within the reproductive system than at the pituitary. These non-mammalian GnRH analogs may be used in pharmaceutical preparations, and specifically in various treatment methods as a contraceptive or post-coital contraceptive agent. The non-mammalian GnRH analogs are also provided in pharmaceutical preparations that may be used clinically for maintaining pregnancy when used in very low doses and administered in pulsatile fashion, as well as in preparations for the treatment of male and female reproductive system disorders. The aza-Gly (10) amide non-mammalian analogs are yet other embodiments of the non-mammalian GnRH analogs provided as a part of the invention.

A method for recognizing and evaluating the presence and function of GnRH receptors on tumor cells originating in the brain and / or nervous system and / or the meninges and / or reactive neuroglia cells and / or primitive neuroectodermal tumor cells and / or on Kaposi sarcoma is provided. Furthermore a method for reducing degenerate GnRH-positive tumor cells and / or for decreasing cellular replication of the above GnRH-positive tumor cells comprising administering to a cell or to a subject a replication decreasing amount of a GnRH agonist and / or GnRH antagonist and / or an erythropoietin agonist, and / or a thrombopoietin agonist, and / or a endothelin antagonist and / or a gonadotropin inhibiting hormone agonist is also provided. Furthermore, a diagnostic kit for detecting GnRH receptors on tumor cells according to the present methods is disclosed.

Specially designed non-mammalian GnRH analogs resistant to degradation by the tumor tissue enzymes, post-proline peptidases as well as endopeptidases, are disclosed. The GnRH analogs are further defined as analogs of chicken II GnRH, salmon GnRH, or herring GnRH, but can include any non-mammalian GnRH analog with similar amino acid structure. These non-mammalian analogs incorporate D-arginine, D-leucine, D-tBu-Serine or D-Trp or other similar amino acids at position 6 and ethylamide or aza-Gly-amide or similar amides at position 10. These analogs demonstrate preferential binding to tumor cell GnRH receptors that is greater relative to the binding of the mammalian analogs to the tumor cell GnRH receptor. These non-mammalian GnRH analogs may be used in pharmaceutical preparations, and it specifically in various treatments as an anti-tumor, anti-proliferation, anti-metastatic and / or an apoptotic agent. The non-mammalian GnRH analogs are also provided in pharmaceutical preparations that may be used clinically for tumor regression when used in very low doses and administered in pulsatile fashion.

The present invention provides a mouse hybrid tumor cell strain (preserving number: ATCC GHR-106PTA-10252) and a monoclonal antibody (GHR-106) of anti-gonadotropin-releasing hormone receptor which is secreted from the mouse hybrid tumor cell strain. The antibody can perform effective inbibitional effect for the tumor cell through combining with the surface receptor of tumor cell. Then the antibody can be used for the diagnosis and treatment process of tumor and the application for preparing the antitumor drug.

Monoclonal antibodies against gonadotropin releasing hormone (GnRH) receptor induce cellular apoptosis of various cancer cells expressing this surface receptor. The monoclonal antibodies and their humanized forms, or fragments thereof, can serve as anti-cancer agents for the treatment of cancer in humans, and can function as analogs of GnRH to affect regulation of reproductive functions or fertility in humans.

Disclosed are a gonadotropin releasing hormone receptor antagonist and a pharmaceutical composition including the same, which can be useful in preventing or treating a sex hormone-related disease such as endometriosis, amenorrhea, irregular menstruation, uterine myoma, uterine fibroids, polycystic ovarian disease, lupus erythematous, hypertrichosis, precocious puberty, short stature, acne, alopecia, gonadal steroid-dependent neoplasms, gonadotropin-producing pituitary adenoma, sleep apnea, irritable bowel syndrome, premenstrual syndrome, benign prostatic hyperplasia, contraception, and infertility, as well as Alzheimer disease.

The invention provides a GnRH (Gonadotropin-releasing hormone) receptor-targeted near-infrared fluorescent imaging probe GnRHa-ICG and a preparation method and application thereof. The GnRH receptor-targeted near-infrared fluorescent imaging probe GnRHa-ICGis formed by coupling a GnRH polypeptide (sequence D-2-Nal-D-4-Cl-Phe-D-3-Pal-Ser-Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH2) and activated near-infraredfluorescent dye ICG-NHS. Based on the principle of specific binding of the GnRH polypeptide to the GnRH receptor, advantages that the GnRH receptor has high expressionin a reproductive system tumor such as ovarian cancer, the near-infrared fluorescent dye ICG penetrates deeper and the background tissue autofluorescence is weaker are utilized, tumor cells and tumor foci which cause high expressionof the GnRH receptor can be targeted and recognized. The GnRHreceptor-targeted near-infrared fluorescent imaging probe GnRHa-ICG has a good application prospect in fluorescence imaging and fluorescence guided surgery.

A method for recognizing and evaluating the presence and function of GnRH receptors on tumor cells including those originating in the brain and / or nervous system and / or the meninges and / or reactive neuroglia cells and / or primitive neuroectodermal tumor cells and / or on Kaposi sarcoma is provided. Furthermore, a method for reducing degenerate GnRH-positive tumor cells and / or for decreasing cellular replication of the above GnRH-positive tumor cells comprising administering to a cell or to a subject a replication decreasing amount of a GnRH agonist and / or GnRH antagonist and / or an erythropoietin agonist, and / or a thrombopoietin agonist, and / or a endothelin antagonist and / or a gonadotropin inhibiting hormone agonist is also provided. Furthermore, a diagnostic kit for detecting GnRH receptors on tumor cells according to the present methods is disclosed.

The present invention relates to Gonadotropin Releasing Hormone (GnRH, also known as Luteinizing Hormone Releasing Hormone) receptor antagonists.

The invention belongs to the field of medicine and chemistry, and relates to a GnRH analogue-cytotoxic molecule conjugate shown in the formula (1), a preparation method thereof, and application thereof in preparation of medicine for treating tumors. The invention further relates to a stereoisomer or solvate or salt without physiological toxicity of the GnRH analogue-cytotoxic molecule conjugate shown in the formula (1), and a medicine composition comprising the compound. Cytotoxic molecules are coupled with a GnRH analogue through a degradable connecting arm, and the obtained GnRH analogue-taxol conjugate can keep high binding activity with a GnRH receptor, has the good plasma stability and tumor cell growth inhibitory activity, and has the good research significance and prospect.

Chicken II and salmon GnRH or its analog decapeptides resistant to degradation by peptidase incorporating D-arginine, D-leucine, D-tBu-Serine, D-Trp or other active D amino acids at position 6 and ethylamide, aza-Gly-amide or other Gly amide at position 10. The non-mammalian GnRH or its analogs demonstrate preferential binding to male and female reproductive system GnRH receptors as well as tumor cell GnRH receptors in these systems. Biopotency is greater within the reproductive system and at tumor cells than at the pituitary. These non-mammalian GnRH or its analogs may be used in pharmaceutical preparations, and specifically in various treatment methods as a contraceptive or post-coital contraceptive agent. The non-mammalian GnRH or its analogs are also provided in pharmaceutical preparations that may be used clinically for maintaining pregnancy when used in very low doses and administered in pulsatile fashion, as well as in preparations for the treatment of male and female reproductive system disorders including cancers of these systems or other system with GnRH II receptors. The aza-Gly (10) amide non-mammalian analogs are yet other embodiments of the non-mammalian GnRH analogs provided as a part of the invention.

The invention provides a GnRH analogs-antineoplastic drug conjugate. The structure of the conjugate is GnRHa-Linker-Dox. The GnRHa is a GnRH analogue. The Linker is a connecting arm and is used for coupling the GnRHa with an antineoplastic drug. The Dox is an antineoplastic drug doxorubicin. The invention further provides a preparation method of the GnRH analogs-antineoplastic drug conjugate and application to drugs for the prevention or treatment of tumors of the GnRH analogs-antineoplastic drug conjugate. The conjugate has good tumor cell selectivity, can target tumor cells which over-express GnRH receptors, and the toxic side effects of the doxorubicin are reduced. The The conjugate lays a foundation for research and development of a new type of anti-tumor drug targeting GnRH receptors,and good application prospects are achieved.

Disclosed are compounds useful as gonadotrophin-releasing hormone (“GnRH”) receptor antagonist.

The present invention relates to Gonadotropin Releasing Hormone (GnRH, also known as Luteinizing Hormone Releasing Hormone) receptor antagonists.

Herein disclosed is a method of rescuing gonadotropin-releasing hormone receptor (GnRHR) mutants with IN3 or a mimetic thereof. IN3 significantly rescues 11 missense mutations as assessed by radioligand binding and by IP production. Such rescue occurred despite widely disparate loci along the receptor. In addition, many altered GnRH receptors (terminally truncated, internal deletions, or lacking the ability to form bridges to form tertiary structure) were rescued with IN3.

The invention discloses a tracer for a derivative based on GnRH polypeptide as well as a preparation method and application thereof. A structural formula of the derivative based on the GnRH polypeptide is as follows: the formula is shown in the description, wherein R is a group containing a tracing atom. The derivative based on the GnRH polypeptide, disclosed by the invention, has good specificity; the intake amount of the derivative in visceral organs is relatively low and the background intake amount is relatively low; meanwhile, the derivative has a relatively high intake amount in tumor tissues in which GnRH receptors are highly expressed; especially, the derivative is suitable for being used as a tumor imaging agent. According to the tracer disclosed by the invention, PET (Polyethylene Terephthalate) imaging and in-vivo stability experiment results of bodies of nude mice bearing tumor show that the tracer has high tumor specificity and in-vivo stability.

The invention relates to a fusion protein mutant capable of directionally killing tumour cells, which consists of an orienting part and an effect part, wherein the orienting part consists of gonadotropin releasing hormone (GnRH), the effect part consists of cytotoxin, and the fusion protein mutant has the characteristics that the tumour cells excessively expressing GnRH receptors can be directionally reached and killed.

The invention relates to application of a pancreatic GnRH receptor function regulator to preparation of drugs used for treating type 2 diabetes. According to the invention, pancreases with normal glucose concentration and pancreases with high-concentration glucose for simulating diabetes are subjected to perfusion of GnRH and a pancreatic GnRH receptor, and results show that pancreatic GnRH with a certain concentration has important regulating effect on the secretion time phase of main hormones of pancreatic islets, i.e., insulin and pancreatic glucagon and that a perfusion solution with certain-concentration GnRH does not inhibit the secretion of pancreatic glucagon, stimulates the secretion of pancreatic glucagon instead and leads to delay of the secretion peak of insulin. Thus, a theoretical and experimental foundation is provided for preparation of drugs for regulating the secretion time phase of insular hormones in virtue of pancreatic GnRH and regulating substances for the receptor approach of pancreatic GnRH and further for preparation of drugs used for restoring inhibition of high glucose on pancreatic glucagon in virtue of pancreatic GnRH and the receptor approach thereof.

The present invention relates to methods of making Gonadotropin Releasing Hormone ('GnRH') (also known as Leutinizing Hormone Releasing Hormone ('LHRH')) receptor antagonists.

Spiroindoline derivatives, processes for their preparation and pharmaceutical compositions thereof, their use for the treatment of diseases, and their use for the manufacture of medicaments for the treatment of diseases, especially sex-hormone-related diseases in both men and women, in particularly those selected from the group of endometriosis, uterine leiomyoma (fibroids), polycystic ovarian disease, menorrhagia, dysmenorrhea, hirsutism, precocious puberty, gonadal steroid-dependent neoplasia such as cancers of the prostate, breast and ovary, gonadotrope pituitary adenomas, sleep apnea, irritable bowel syndrome, premenstrual syndrome, benign prostatic hypertrophy, contraception, infertility and assisted reproductive therapy such as in vitro fertilization. The present application relates in particular to spiroindoline derivatives as gonadotropin-releasing hormone (GnRH) receptor antagonists.

The present invention relates to a method for searching myelin using gonadotropin-releasing hormone receptors (GnRH-R) as a biomarker, more precisely, a method for investigating the distribution of myelin by immunohistochemical staining using GnRH-R antibody, based on the fact that GnRH-R and myelin are observed in the same region. The method for searching myelin of the invention can contribute to the studies on demyelination related degenerative brain disease and the disclosure of functions of myelin and the relation of myelin and GnRH-R.