15 results about "Indolamines" patented technology

Disclosed herein is a molecule, or a pharmaceutically acceptable salt thereof, that has a formula M1DO1-L-ME3, M1DO1 is a moiety that binds to IDO1, L is a linker covalently attaching M1DO1 and ME3, and ME3 is a moiety that binds to an E3 ubiquitin ligase. Disclosed herein are also the uses of the molecule, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same, in a method of treating cancer in a subject in need thereof.

This disclosure provides a method for treating a cancer patient comprising administering to the patient a therapeutically effective amount of an anti-PD-1 antagonist, for example, an anti-PD-1 or anti-PD-L1 antibody, in combination with an indolamine 2,3-dioxygenase inhibitor, wherein the patient is identified as exhibiting a combined biomarker comprising (a) a high IFNγ inflammatory signature score and (b) a low tryptophan 2,3-dioxygenase 2 (TDO2) gene expression score. The high IFNγ inflammatory signature score is determined by measuring the expression of a panel of IFNγ-related inflammatory genes in a cancer sample obtained from the patient, wherein the gene panel comprises, for example, IFNγ, CXCL10, CXCL9, HLA-DRA, IDO1, and STAT1. In some respects, the gene panel also includes CCR5, CXCL11, GZMA, and PRF1.In some aspects, the genetic panel comprises CXCR6, TIGIT, PD-L1, PD-L2, LAG3, NKG7, PSMB10, CMKLR1, CD8A, IDO1, CCL5, CXCL9, HLA.DQA1, CD276, HLA.DRB1, STAT1, HLA.E and TDO2.

The disclosure provides a method for treating a subject afflicted with a cancer comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antagonist, e.g., an anti-PD-1 or anti-PD-L1 antibody, in combination with an indoleamine 2,3-dioxygenase inhibitor, wherein the subject is identified as exhibiting a combined biomarker comprising (a) a high IFNγ inflammatory signature score and (b) a low tryptophan 2,3-dioxygenase 2 (TDO2) gene expression score. The high IFNγ inflammatory signature score is determined by measuring the expression of a panel of IFNγ related inflammatory genes in a cancer sample obtained from the subject, wherein the gene panel comprises, e.g., IFNγ, CXCL10, CXCL9, HLA-DRA, IDO1, and STAT1. In some aspects, the gene panel further comprises CCR5, CXCL11, GZMA, and PRF1. In some aspects, the gene panel comprises CXCR6, TIGIT, PD-L1, PD-L2, LAG3, NKG7, PSMB10, CMKLR1, CD8A, IDO1, CCL5, CXCL9, HLA.DQA1, CD276, HLA.DRB1, STAT1, HLA.E, and TDO2.

According to the IDO1 activity detection method provided by the invention, by adding exogenous tryptophan and optimizing experimental parameters such as the cell inoculation amount, the cell culture time and the IFN-gamma concentration, the activity of IDO1 enzyme generated by the mesenchymal stem cells is more accurately measured, so that the immune regulation and control capability of the mesenchymal stem cells is more accurately evaluated.

Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme: Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.

Indoleamine 2,3-dioxygenase 1 (IDO1) and / or tryptophan 2,3-dioxygenase (TDO) inhibitors and methods of using same. The inhibitors can be used in methods of inhibiting IDO1 and / or TDO, either in vivo or in vitro. The inhibitors of the invention can also be used in methods of treating IDO1- and TDO-mediated conditions, such as cancer and neuropathic pain.

The present invention provides a novel compound having a cyclohexyl-(alkyl- or cycloalkyl-substituted)ethylene-amino-heteroaryl moiety or a pharma- ceutically acceptable salt thereof, a method for preparing the compound, a pharmaceutical composition containing the compound, and use of the compound. The compound or a pharma- ceutically acceptable salt thereof not only has excellent inhibitory activity against indoleamine-2,3-dioxygenase (IDO), but also shows a remarkably high in vivo exposure upon oral administration. Therefore, the compound or a pharma- ceutically acceptable salt thereof can be usefully applied to the prevention or treatment of various diseases associated with IDO.

The present invention relates to novel pyrrolidine-fused myrtanol derivatives (or 4-azatricyclo[6.1.1.02,6]decanes) of the general formula (I) or pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions comprising such compounds as well as their use as medicaments, especially in methods for the prophylaxis or treatment of a disease and / or a disorder caused by and / or associated with indolamine 2,3-dioxygenase 1 (1001) selected from: an inflammatory condition, an infectious disease, a cancer, a central nervous system disease or disorder, a disease or disorder relating to female reproductive health, coronary heart disease, chronic renal failure, post anaesthesia cognitive dysfunction, and cataracts.

Provided herein are compounds, salts, crystalline forms, and pharmaceutical compositions that are related to IDO inhibitors, in particular, Compound 1,1-(5-((4-chlorophenyl)amino)-6-(ethyl(tetrahydro-2H-pyran-4-yl)amino)pyridin-3-yl)cyclobutane-1-carboxylic acid. Also provided are methods of treating a disease or disorder such as a cancer or infectious disease that comprises administering to a subject in need thereof one or more of the compounds or compositions of the present disclosure.

The present application provides a compound having a cyclohexyl-(alkyl or cycloalkyl-substituted)ethylene-amino-heteroaryl moiety or a pharmaceutically acceptable salt thereof, a preparation method thereof, a pharmaceutical composition comprising the same, and a use thereof. The compound or the pharmaceutically acceptable salt thereof not only has excellent inhibitory activity against indoleamine 2,3-dioxygenase (IDO), but also exhibits significantly high in vivo exposure after oral administration. Accordingly, the compound or the pharmaceutically acceptable salt thereof can be effectively applied to the prevention or treatment of various diseases associated with IDO.

The present disclosure generally relates to the treatment of subjects having IBD or at risk of developing IBD by administering an Indoleamine 2,3-Dioxygenase 2 (IDO2) agonist or a SMAD Family Member 2 (SMAD2) agonist to the subject.

Provided in the present invention is a method for detecting IDO1 activity. By means of the addition of exogenous tryptophan and the optimization of experimental parameters such as the cell inoculation size, cell culture time and IFN-γ concentration, the method realizes more accurate determination of the activity of an IDO1 enzyme produced by mesenchymal stem cells, thereby enabling more accurate evaluation of the immunomodulatory capacity of mesenchymal stem cells.

The invention relates to an application of an indoleamine 2, 3-dioxygenase 1 inhibitor in preparation of a medicine for treating cancer cachexia. The indoleamine 2, 3-dioxygenase 1 is determined as a core therapeutic target of cancer cachexia for the first time, and it is proved that palmatine hydrochloride shows an exact therapeutic effect in cell and animal models through a multi-channel synergistic mechanism of metabolic reprogramming, protein degradation inhibition, anabolism signal recovery and muscle regeneration promotion. And sufficient experimental basis and theoretical support are provided for clinical transformation.

Provided is a quinoline derivative having indoleamine-2,3-dioxygenase inhibitory activity, specifically, provided is a compound of general Formula (I) or pharmaceutically acceptable salt thereof, its pharmaceutical composition, preparation method and use in the manufacture of a medicament for immunomodulating and preventing and / or treating of a disease associated with IDO expression abnormality and / or tryptophan metabolism abnormality. Also provided is use of a combination medication of the quinoline derivative and HDAC inhibitor and its use in the manufacture of an anti-tumor drug.A-X—B—Y-M   Formula (I)