24 results about "Indolamines" patented technology

The present disclosure relates in some aspects to constructs and methods for increasing solid organ transplant survival. More specifically, aspects of the present disclosure relate to methods and constructs for administering full-length PD-L1 and one immune modulators, such as one or more of: CTLA-4, Qa-1d, HLA-E, HLA-G, CMTM6, and Indolamine-2,3-dioxygenase (IDO), by ex vivo perfusion in order to increase solid organ transplant survival.

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.

Indoleamine 2,3-dioxygenase (IDO) is a heme-binding enzyme involved in pathophysiological processes including, but not limited to, antimicrobial and antitumor defense, neuropathology, immunoregulation, and antioxidant activity. Aspects of the disclosure relate to variants of IDO that comprise one or more amino acid variations relative to a wild-type IDO and / or that are connected to a synthetic polymer, such as poly (ethylene glycol). Embodiments of the disclosure provide variant IDOs that have improved properties, such as resistance to oxidative conditions, protein solubility, lower propensity to aggregate in vivo, increased half-life in the circulatory system upon administration to a subject, increased binding to a cell or tissue, or any combination thereof. Accordingly, IDO variants of the disclosure can be administered to a subject in need thereof, such as a subject having, suspected of having, or at risk of developing a disease, disorder, or condition, such as one associated with inflammation.

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.

The present disclosure provides dual functioning compounds, compositions, formulations, and methods for inducing or modulating an immune or inflammatory response and treating diseases or disorders (e.g., cancer, autoimmune diseases, inflammatory diseases, and infectious diseases) with the compounds or compositions thereof. In particular disclosed herein are dual functioning compounds comprising a stimulator of interferon (IFN) genes (STING) agonist moiety and a second active moiety selected from an indoleamine 2,3-dioxygenase (IDO) inhibitor and phosphatidylinositol 3-kinase (PI3K) inhibitor, and compositions and formulations thereof.

The invention relates to the field of prophylaxis and therapy of cancer. Provided is a Indoleamine 2,3-dioxygenase (IDO) or peptide fragments hereof that are capable of eliciting anti-cancer immune responses. Specifically, the invention relates to the use of IDO or peptides derived herefrom or IDO specific T-cells for treatment of cancer. The invention thus relates to an anti-cancer vaccine which optionally may be used in combination with other immunotherapies and to IDO specific T-cells adoptively transferred or induced in vivo by vaccination as a treatment of cancer. The invention also provides that the medicaments herein provided may be used in combination with cancer chemotherapy treatment. The invention further provides the prophylaxis and therapy of infections by the same means as described above. The use of IDO and immunogenic peptide fragments hereof in cancer and infection treatment, diagnosis and prognosis is also provided.

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.

The invention discloses synthesis of a benzisothiazolinone compound with indoleamine 2, 3-dioxygenase IDO1 (indoleamine 2, 3-dioxygenase) inhibitory activity and application of the benzisothiazolinone compound in preparation of antitumor drugs. The structural general formula of the inhibitor is as shown in formula (1). Pharmacological experiments show that the compound provided by the invention not only has low cytotoxicity, but also shows good IDO1 inhibitory activity, and has relatively good inhibitory activity on lung cancer paclitaxel drug-resistant cell strains. In addition, an AhR activation experiment shows that the compound disclosed by the invention is not strong in AhR activation activity. In-vivo experiments show that the compound has no obvious acute toxicity, is safe to take orally and can be applied to preparation of antitumor drugs for inhibiting IDO1-mediated tryptophan metabolic pathways.

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.

To provide a mesenchymal stem cell (MSC) secretome composition.SOLUTION: An MSC secretome composition comprises: i. less than about 250 μM IDO (Indoleamine-2,3-dioxygenase) enzyme activity; ii. at least one trophic factor or cytokine selected from the group consisting of HGF, FGF-7, TIMP-1, TIMP-2, PAI-1 (Serpin E1), VEGF-A, and / or b-NGF; iii. at least one additional factor selected from the group consisting of sFLT-1, PEDF (Serpin F1), Serpin A1, IGFBP-2, and the like; and iv. at least one additional factor selected from the group consisting of DPPIV (dipeptidyl peptidase-4), uPA, Angiopoietin-1, and the like.SELECTED DRAWING: Figure 1

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.

The present application discloses an indoleamine-2,3-dioxygenase inhibitor and a preparation method thereof. The inhibitor of the present application has a structure as shown in general formula (I), wherein Ar, E, Y, X, V, D, W, B, ring A and ring B are defined in the description and claims. The present application also discloses a preparation method of the inhibitor. The compound of general formula (I) of the present application can be used as an indoleamine-2,3-dioxygenase inhibitor to prepare a medicine for preventing and / or treating an indoleamine-2,3-dioxygenase mediated disease.

The present application provides quinoline derivatives having indoleamine-2,3-dioxygenase inhibitory activity, in particular, the present application provides compounds of general formula (I) or pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, methods of preparation and uses in the manufacture of immunomodulatory and prophylactic and / or therapeutic agents for diseases associated with abnormal expression of IDO and / or abnormal tryptophan metabolism. The present application also relates to the combination of the quinoline derivatives with HDAC inhibitors and their use in the manufacture of anti-tumor agents.

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.

The invention relates to a drug delivery system based on dendritic cell exosomes as well as a preparation method and application of the drug delivery system. The drug delivery system comprises a dendritic cell-derived exosome, an indoleamine 2, 3-dioxygenase inhibitor wrapped in the exosome, and a death receptor monoclonal antibody modified on the surface of the exosome. The death receptor monoclonal antibody is connected with a coupling agent to modify the surface of the exosome. The drug delivery system carries the indoleamine 2, 3-dioxygenase inhibitor to inhibit the conversion of tryptophan and relieve the malignant melanoma immunosuppression microenvironment, and specifically targets a death receptor on the surface of a malignant melanoma cell by loading the death receptor monoclonal antibody, so that the targeting property of the delivery system is enhanced.

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)