42 results about "Type i receptor" patented technology

The present invention provides compositions and methods of use of anti-IGF-1R antibodies or antibody fragments. Preferably the antibodies bind to IGF-1R but not IR; are not agonists for IGF-1R; do not block binding of IGF-1 or IGF-2 to isolated IGF-1R, but effectively neutralize activation of IGF-1R by IGF-1 in intact cells; and block binding of an R1 antibody to IGF-1R. The antibodies may be murine, chimeric, humanized or human R1 antibodies comprising the heavy chain CDR sequences DYYMY (SEQ ID NO:1), YITNYGGSTYYPDTVKG (SEQ ID NO:2) and QSNYDYDGWFAY (SEQ ID NO:3) and the light chain CDR sequences KASQEVGTAVA (SEQ ID NO:4), WASTRHT (SEQ ID NO:5) and QQYSNYPLT (SEQ ID NO:6). Preferably the antibodies bind to an epitope of IGF-1R comprising the first half of the cysteine-rich domain of IGF-1R (residues 151-222). The anti-IGF-1R antibodies may be used for diagnosis or therapy of various diseases such as cancer.

The present invention relates to the treatment of hypertension and type 2 diabetes, Metabolic Syndrome or a pre-diabetic state, by the administration of a therapeutically effective amount of a combination of a dual PPARα / γ agonist and an Angiotensin II type I receptor antagonist, including pharmaceutically acceptable salts and solvates of said active ingredients.

This invention is directed to mutated Activin A type I receptor proteins (ACVR1) and isolated nucleic acids encoding same. The invention also relates to the use of mutated ACVR1 in the diagnosis and treatment of Fibrodysplasia Ossificans Progressiva (FOP).

A thiazolylimidazole derivative represented by the formula or a pharmaceutically acceptable salt thereof, and an ALK5 inhibitor, an therapeutic agent for alopecia or a hair growth agent having the above as an active ingredient, wherein: X1 and X2 are different from each other and represent a sulfur atom or a carbon atom; R1 represents a phenyl group; a substituted phenyl group; a phenyl group condensed with a hetero aromatic ring; a pyridyl group; or a pyridyl group condensed with a hetero aromatic ring; R2 represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms substituted with 1 to 5 halogen atoms, an alkoxy group having 1 to 6 carbon atoms, an alkanoyl group having 1 to 5 carbon atoms, or a hydroxyalkyl group having 1 to 6 carbon atoms, A represents a group which is represented by the formula. The present invention provides an inhibitory substance against ALK5 which is a TGF-β type I receptor and provides a hair growth stimulant or a hair growth agent based on its novel activities.

Disclosed are novel quinazoline derivatives containing phosphorus substitutions and methods for the treatment of hyperproliferative diseases (e.g. cancer) using the compounds. These compounds are type I receptor protein kinase inhibitors useful in treating disorders related to abnormal protein kinase activities such as cancer and inflammation in mammals. Also disclosed are pharmaceutical compositions containing the compounds, methods for the preparation of the compounds and their pharmaceutically acceptable salts.

This invention relates to 2-pyridyl substituted imidazoles which are inhibitors of the transforming growth factor-β (TGF-β) type I receptor (ALK5) and / or the activin type I receptor (ALK4), methods for their preparation, and their use in medicine, specifically in the treatment and prevention of a disease state mediated by these receptors.

The present invention relates to differentiation of stem cells into a homogeneous endocrine progenitor cell population suitable for further differentiation into pancreatic beta-cells. The present invention provides methods for obtaining NGN3 / NKX2.2 double positive endocrine progenitor cells by exposing precursor cells to a TGF-β type I receptor inhibitor, a BMP antagonist, an adenylate cyclase activator and nicotinamide and / or exposing to the precursor cells to a selection of small molecules.

This invention provides quinazoline analogs of Formula I:where A is bonded to at least one of the carbons at the 5, 6, 7 or 8 position of the bicyclic ring, and the ring is substituted by up to two independent R3 groups. The invention also includes methods of using compounds of Formula I as type I receptor tyrosine kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.

This invention provides compounds of Formula Iwherein B, G, A, E, R1, R2, R3, m and n are as defined herein, which are useful as type I receptor tyrosine kinase inhibitors, and methods of use thereof in the treatment of hyperproliferative disorders in mammals.

This invention concerns quinazoline analogs of Formula I: where an A group is bonded to at least one of the carbons at the 5, 6, 7 or 8 position of the bicyclic ring, and the ring is substituted by up to three independent R3 groups. The invention also includes methods of using these compounds as type I receptor tyrosine kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.

This invention is directed to mutated Activin A type I receptor proteins (ACVR1) and isolated nucleic acids encoding same. The invention also relates to compositions and methods for siRNA-based regulation of mutated ACVR1 expression in the treatment of Fibrodysplasia Ossificans Progressiva (FOP).

This invention concerns quinazoline analogs of Formula I:where an A group is bonded to at least one of the carbons at the 5, 6, 7 or 8 position of the bicyclic ring, and the ring is substituted by up to three independent R3 groups. The invention also includes methods of using these compounds as type I receptor tyrosine kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.

This invention relates to use of inhibitors of the transforming growth factor-β (TGF-β) type I receptor (ALK5) and / or the activin type I receptor (ALK4) in treating, preventing, or reducing fibrosis, cancer, and vascular injuries.

A thiazolylimidazole derivative represented by the formula (I) or a pharmaceutically acceptable salt thereof, and an ALK5 inhibitor, an therapeutic agent for alopecia or a hair growth agent having the above as an active ingredient, wherein: X 1 and X 2 are different from each other and represent a sulfur atom or a carbon atom; R 1 represents a phenyl group; a substituted phenyl group; a phenyl group condensed with a hetero aromatic ring; a pyridyl group; or a pyridyl group condensed with a hetero aromatic ring; R 2 represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms substituted with 1 to 5 halogen atoms, an alkoxy group having 1 to 6 carbon atoms, an alkanoyl group having 1 to 5 carbon atoms, or a hydroxyalkyl group having 1 to 6 carbon atoms, A represents a group which is represented by the formula (II). The present invention provides an inhibitory substance against ALK5 which is a TGF- type I receptor and provides a hair growth stimulant or a hair growth agent based on its novel activities.

This invention relates to 2-pyridyl substituted imidazoles which are inhibitors of the transforming growth factor-β (TGF-β) type I receptor (ALK5) and / or the activin type I receptor (ALK4), methods for their preparation, and their use in medicine, specifically in the treatment and prevention of a disease state mediated by these receptors.

The invention relates to the cloning of a transforming growth factor-beta (TGF-beta) superfamily type I receptor gene Tgfbrl1 of chlamys farreri in a molecular genetic marker technology, a screening and typing technology of a single nucleotide polymorphism (SNP) locus which is relevant with the weight of adductor muscles in the gene and a method for the application of the gene to the breeding of the high-yield chlamys farreri. A total-length complementary deoxyribonucleic acid (cDNA) sequence of the Tgfbr1 gene of the chlamys farreri is obtained by utilizing a homology-based cloning strategy; an SNP lotus is discovered by blastn comparison, and primers and a probe are designed for the locus; and SNP typing is performed in a natural population of the chlamys farreri by using a high-resolution melting curve technology, and the weight of the adductor muscle of an individual is measured. Statistic analysis displays that the loci c.1815C>T are obviously relevant with the weight of the adductor muscles of the chlamys farreri, and the weight of the adductor muscles of individuals with TT genetypes is obviously higher than that of the adductor muscles of individuals with CC and CT genetypes. In the selective breeding process of the high-yield chlamys farreri, the breeding candidate colonies of the chlamys farreri can be subjected to c.1815C>T typing, and the individuals of which the loci c.1815C>T are TT genetypes are used as a breeding parent preferably by combining typing information of other loci which are relevant with growth properties.

This invention is directed to mutated Activin A type I receptor proteins (ACVR1) and isolated nucleic acids encoding same. The invention also relates to compositions and methods for siRNA-based regulation of mutated ACVR1 expression in the treatment of Fibrodysplasia Ossificans Progressiva (FOP).

The present invention provides a novel 2-pyridyl substituted imidazole derivative, or a pharmaceutically acceptable salt or solvate thereof, which selectively inhibits the transforming growth factor-β (TGF-β) type I receptor (ALK5) and / or the activin type I receptor (ALK4); a pharmaceutical composition comprising same as an active ingredient; and a use of the 2-pyridyl substituted imidazole derivative for the manufacture of a medicament for preventing or treating a disease mediated by ALK5 and / or ALK4 receptors in a mammal.

This invention provides compounds of Formula Iwherein B, G, A, E, R1, R2, R3, m and n are as defined herein, which are useful as type I receptor tyrosine kinase inhibitors, and methods of use thereof in the treatment of hyperproliferative disorders in mammals.

A thiazolylimidazole derivative represented by the formulaor a pharmaceutically acceptable salt thereof, and an ALK5 inhibitor, an therapeutic agent for alopecia or a hair growth agent having the above as an active ingredient,wherein:X1 and X2 are different from each other and represent a sulfur atom or a carbon atom; R1 represents a phenyl group; a substituted phenyl group; a phenyl group condensed with a hetero aromatic ring; a pyridyl group; or a pyridyl group condensed with a hetero aromatic ring; R2 represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms substituted with 1 to 5 halogen atoms, an alkoxy group having 1 to 6 carbon atoms, an alkanoyl group having 1 to 5 carbon atoms, or a hydroxyalkyl group having 1 to 6 carbon atoms, A represents a group which is represented by the formula.The present invention provides an inhibitory substance against ALK5 which is a TGF-β type I receptor and provides a hair growth stimulant or a hair growth agent based on its novel activities.

The present invention provides compositions and methods of use of anti-IGF-1R antibodies or antibody fragments. Preferably the antibodies bind to IGF-1R but not IR; are not agonists for IGF-1R; do not block binding of IGF-1 or IGF-2 to isolated IGF-1R, but effectively neutralize activation of IGF-1R by IGF-1 in intact cells; and block binding of an R1 antibody to IGF-1R. The antibodies may be murine, chimeric, humanized or human R1 antibodies comprising the heavy chain CDR sequences DYYMY (SEQ ID NO:1), YITNYGGSTYYPDTVKG (SEQ ID NO:2) and QSNYDYDGWFAY (SEQ ID NO:3) and the light chain CDR sequences KASQEVGTAVA (SEQ ID NO:4), WASTRHT (SEQ ID NO:5) and QQYSNYPLT (SEQ ID NO:6). Preferably the antibodies bind to an epitope of IGF-1R comprising the first half of the cysteine-rich domain of IGF-1R (residues 151-222). The anti-IGF-1R antibodies may be used for diagnosis or therapy of various diseases such as cancer.

This invention relates to 2-pyridyl substituted imidazoles which are inhibitors of the transforming growth factor-β (TGF-β) type I receptor (ALK5) and / or the activin type I receptor (ALK4), methods for their preparation, and their use in medicine, specifically in the treatment and prevention of a disease state mediated by these receptors.

The present invention provides a novel 2-pyridyl substituted imidazole derivative, or a pharmaceutically acceptable salt or solvate thereof, which selectively inhibits the transforming growth factor-β (TGF-β) type I receptor (ALK5) and / or the activin type I receptor (ALK4); a pharmaceutical composition comprising same as an active ingredient; and a use of the 2-pyridyl substituted imidazole derivative for the manufacture of a medicament for preventing or treating a disease mediated by ALK5 and / or ALK4 receptors in a mammal.

This invention relates to use of inhibitors of the transforming growth factor-β (TGF-β) type I receptor (ALK5) and / or the activin type I receptor (ALK4) in treating, preventing, or reducing fibrosis, cancer, and vascular injuries.

This invention is directed to mutated Activin A type I receptor proteins (ACVR1) and isolated nucleic acids encoding same. The invention also relates to the use of mutated ACVR1 in the diagnosis and treatment of Fibrodysplasia Ossificans Progressiva (FOP).

The invention provides a high-throughput screening method for screening a vasoactive intestinal peptide I type receptor inhibitor; in experiments, with use of coupling of a vasoactive intestinal peptide type I receptor and a Gs protein, AC is activated, the cAMP content is increased, a product with fluorescence can be produced, the role of the vasoactive intestinal peptide type I receptor is judged by the fluorescence intensity, and thus whether the obtained compound has an inhibitory effect of the vasoactive intestinal peptide type 1 receptor is obtained. The method comprises the following steps: 1) establishment and optimization of a screening model of the vasoactive intestinal peptide I type receptor inhibitor: determining the most suitable concentration for a reaction of VIP and vasoactive intestinal peptide I type receptor cells; and 2) model reliability verification with positive drug: verifying that a positive drug IC50 is in accordance with that of a reference. The method has the advantages that the method is simple and fast, sensitivity of the fluorescence detection value is high, detection accuracy is increased, the result is stable and reliable, and the reappearance is good.

In ovarian carcinoma, Müllerian Inhibiting Substance (MIS) type II receptor (MISRII) and the MIS / MISRII signaling pathway are potential therapeutic targets. Conversely, the role of the three MIS type I receptors (MISRI; ALK2, ALK3 and ALK6) in this cancer needs to be clarified. Using four ovarian cancer cell lines and ovarian cancer cells isolated from patients' tumor ascites, the inventors found that ALK2 and ALK3 are the two main MISRIs involved in MIS signaling at low and high MIS concentrations, respectively. Moreover, high MIS concentrations were associated with apoptosis and decreased clonogenic survival, whereas low MIS concentrations improved cancer cell viability. Finally, the inventors showed that anti-MIS antibody B10 inhibited MIS pro-survival effect. These last results open the way to an innovative therapeutic approach to suppress MIS proliferative effect, instead of administering high doses of MIS to induce cancer cell apoptosis.

The invention relates to the cloning of a transforming growth factor-beta (TGF-beta) superfamily type I receptor gene Tgfbrl1 of chlamys farreri in a molecular genetic marker technology, a screening and typing technology of a single nucleotide polymorphism (SNP) locus which is relevant with the weight of adductor muscles in the gene and a method for the application of the gene to the breeding of the high-yield chlamys farreri. A total-length complementary deoxyribonucleic acid (cDNA) sequence of the Tgfbr1 gene of the chlamys farreri is obtained by utilizing a homology-based cloning strategy; an SNP lotus is discovered by blastn comparison, and primers and a probe are designed for the locus; and SNP typing is performed in a natural population of the chlamys farreri by using a high-resolution melting curve technology, and the weight of the adductor muscle of an individual is measured. Statistic analysis displays that the loci c.1815C>T are obviously relevant with the weight of the adductor muscles of the chlamys farreri, and the weight of the adductor muscles of individuals with TT genetypes is obviously higher than that of the adductor muscles of individuals with CC and CT genetypes. In the selective breeding process of the high-yield chlamys farreri, the breeding candidate colonies of the chlamys farreri can be subjected to c.1815C>T typing, and the individuals of which the loci c.1815C>T are TT genetypes are used as a breeding parent preferably by combining typing information of other loci which are relevant with growth properties.