50 results about "Tryptophan Metabolism" patented technology

The invention relates to a preparation method of tryptanthrin compound and a new application of tryptanthrin compound in preparing indoleamine-2,3-dioxygenase (IDO) inhibitor, in particular to an application of tryptanthrin compound in preparing IDO inhibitor and in preparing medicine for preventing and / or treating diseases having pathological characteristics of tryptophan metabolic disturbance mediated by IDO. The structure of the tryptanthrin compound is shown in formula A in the description, wherein R1 and R2 are respectively and independently selected from hydrogen, nitryl, C1 to C5 alkyl, halogen or piperazinyl. The tryptanthrin compound can be used as an IDO inhibitor with high activity and is used for treating diseases having pathological characteristics of tryptophan metabolic disturbance mediated by IDO such as tumor, cancer, Alzheimer disease, autoimmune disease, cataract, mental block, tristimania, anxiety neurosis, acquired immure deficiency syndrome (AIDS) and other serious diseases, and as a medicinal resource which is very difficult to get, the tryptanthrin compound has good potential on researching and developing new medicine.

The invention relates to novel application of berberine and derivatives thereof in preparation of medicines, in particular to application of berberine and derivatives thereof in preparation of indole amine 2, 3-dioxygenase IDO inhibitor, belonging to the medicine field. According to IDO inhibition activity detection, reversible inhibition judgment, inhibitor type judgment, Ki value determination and median effective inhibition concentration IC50 determination, the results show that berberine is reversible inhibitor and inhibition constant Ki is 8muM; and jatrorrhizine hydrochloride and palmatine hydrochloride are irreversible inhibitors, and the median effective inhibition concentrations IC50 thereof are respectively 123muM and 126muM. When the berberine and the derivatives thereof disclosed in the invention are used as IDO inhibitors, the application prospect is wide and the IDO inhibitors can be used for treating serious diseases such as cancers, AIDS, Alzheimer diseases, tristimania, cataract and the like with pathological feature of IDO-mediated tryptophan metabolism.

The invention belongs to the medicinal field, and concretely relates to a use of a 8-nitrotryptanthrin compound as an IDO inhibitor. The 8-nitrotryptanthrin compound is a reversible IDO inhibitor, has an inhibition constant Ki of 0.054muM, has in-vitro and cell-based median effective inhibition concentrations IC50 of 0.103muM and 1.80*10<-5>muM respectively, and has an inhibition effectiveness obviously better than a present inhibitor 1-methyltryptophan (Ki of 34muM and IC50 of 340muM). 8-nitrotryptanthrin disclosed in the invention can effectively lower the abnormally-increasing IDO activity in a tumor animal model as the IDO inhibitor, and also has tumor treatment effects comprising tumor growth delaying, tumor volume reduction and in-vitro tumor cell killing. 8-nitrotryptanthrin disclosed in the invention has a wide application prospect, and can be used for treating serious diseases having the IDO mediated tryptophan metabolism approach pathology characteristics, such as cancers, the Alzheimer disease, tristimania, cataract and the like as the IDO inhibitor.

Multimeric tryptophan biosensors are disclosed, which comprise tryptophan-binding domains conjugated to donor and fluorescent moieties that permit detection and measurement of Fluorescence Resonance Energy Transfer upon tryptophan binding. Such biosensors are useful for real time monitoring of tryptophan metabolism in living cells.

Presently provided are inhibitors of IDO and TDO and pharmaceutical compositions thereof, useful for modulating an activity of indoleamine 2,3-dioxygenase and tryptophan 2,3 dioxygenase; treating immunosuppression; treating a medical conditions that benefit from the inhibition of tryptophan degradation; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosuppression associated with an infectious disease.

The unexpected expression of tryptophan 2,3-dioxygenase (TDO2) in cancer cells and tumors has been established. Methods for diagnosing cancer based on the expression of TDO2 are provided, as are methods for treating cancer and inhibiting the growth of cancer cells by inhibiting TDO2, as well as pharmaceutical compositions.

The invention relates to a preparation method of tryptanthrin compound and a new application of tryptanthrin compound in preparing indoleamine-2,3-dioxygenase (IDO) inhibitor, in particular to an application of tryptanthrin compound in preparing IDO inhibitor and in preparing medicine for preventing and / or treating diseases having pathological characteristics of tryptophan metabolic disturbance mediated by IDO. The structure of the tryptanthrin compound is shown in formula A in the description, wherein R1 and R2 are respectively and independently selected from hydrogen, nitryl, C1 to C5 alkyl, halogen or piperazinyl. The tryptanthrin compound can be used as an IDO inhibitor with high activity and is used for treating diseases having pathological characteristics of tryptophan metabolic disturbance mediated by IDO such as tumor, cancer, Alzheimer disease, autoimmune disease, cataract, mental block, tristimania, anxiety neurosis, acquired immure deficiency syndrome (AIDS) and other serious diseases, and as a medicinal resource which is very difficult to get, the tryptanthrin compound has good potential on researching and developing new medicine.

The invention relates to fused imidazole compounds, and a preparation method and application thereof. The structure of the compounds is shown in a general formula I, wherein the definitions of each group are as described in the specification. The compounds are capable of selectively inhibiting indoleamine 2,3-dioxygenase (IDO). The compounds provided by the invention can be used as IDO inhibitorsfor the treatment and / or prevention of diseases with the pathological characteristics of IDO mediated tryptophan metabolism pathways, such as cancer, eye diseases, autoimmune diseases, psychological disorders, depression, anxiety and other diseases.

The present invention relates to an N-benzyl tryptanthrin derivative, and preparation method and use thereof. The N-benzyl tryptanthrin derivative of the present invention is characterized in that the derivative has a structural general formula as represented by formula 1, wherein each group is defined as in the specification. The preparation method of the compound is simple, has mild conditions and high yield, and is suitable for industrial production. The N-benzyl tryptanthrin derivative has good indoleamine-2,3-dioxygenase (IDO) inhibitory activity, and can be used for treating diseases having the pathological feature of IDO-mediated tryptophan metabolism.

The invention discloses an application of azatryptanthrin derivatives as IDO1 (indoleamine 2,3-dioxygenase) and / or TDO (tryptophan 2,3-dioxygenase) inhibitors. The structure of the derivatives is shown as the general formula (I) in the description, wherein substituents are defined in detail in the description. The compounds shown as the general formula (I) have an inhibition effect on IDO1 and / or TDO and can be used for treating diseases having pathological characteristics of IDO1 and / or TDO mediated tryptophan metabolism, and the diseases include but are not limited to tumors, autoimmune diseases, infectious diseases, Alzheimer disease, depression and anxiety disorder.

The invention discloses indazole compounds as shown in a formula (i) or (II) which is described in the specification, and a preparation method thereof, and application of the compounds as IDO inhibitors. The compounds provided by the invention can be used for preventing and / or treating a plurality of diseases, such as Alzheimer's disease, cataract, infections related to cellular immune activation,autoimmune diseases, AIDS, cancers, depression, the metabolic disorder of tryptophan or the like.

The invention discloses 1H-indazole derivatives and a preparation method thereof, and application of the derivatives as IDO inhibitors. The derivatives provided by the invention can be used for preventing and / or treating a plurality of diseases, such as Alzheimer's disease, cataract, infections related to cellular immune activation, autoimmune diseases, AIDS, cancers, depression or the metabolic disorder of tryptophan.

The invention discloses the use of azatryptanthin derivatives as IDO1 and / or TDO inhibitors. The derivatives are represented by the general formula (I), wherein the definition of each substituent is detailed in the description. The compound represented by the general formula (I) has inhibitory effect on indoleamine-2,3-dioxygenase 1 (IDO1) and / or tryptophan-2,3-dioxygenase (TDO), and can be used For the treatment of diseases with pathological features of tryptophan metabolism mediated by IDO1 and / or TDO, including but not limited to tumors, autoimmune diseases, infectious diseases, Alzheimer's disease, depression, anxiety.

The embodiment of the invention relates to application of a mycotoxin biodegradation agent to promotion of healthy pig production, in particular to application of the mycotoxin biodegradation agent tothe preparation of feed for positively regulating a microbial flora in contents of pig jejunum, improving the detoxification ability of pigs and promoting healthy growth. The mycotoxin biodegradationagent can up-regulate the expression of 153 proteins in the liver of piglets and down-regulate the expression of 55 proteins. The differential proteins are mainly involved in the composition of cellcomponents, molecular functions and biological processes. Analysis of KEGG pathways of the differential proteins shows that the mycotoxin biodegradation agent can up-regulate the expression of 13 proteins without down-regulated proteins, the KEGG pathways in which the up-regulated proteins mainly participate include endoplasmic reticulum protein processing, glycolysis / gluconeogenesis, tryptophan metabolism, valine, leucine and isoleucine metabolism, microbial metabolism in different environments, starch and sucrose metabolism and the like.

The invention discloses nitrogen substituent-containing indazole compounds as shown in a formula (I) which is described in the specification, a preparation method for the compounds, and application ofthe compounds as IDO inhibitors. The compounds provided by the invention can be used for preventing and / or treating a plurality of diseases, such as Alzheimer's disease, cataract, infections relatedto cellular immune activation, autoimmune diseases, AIDS, cancers, depression, the metabolic disorder of tryptophan or the like.

The invention discloses uses of pyridino[3,4-b]indol derivatives in preparation of IDO inhibitor medicines. A compound in the invention can be used for preventing and / or treating various diseases such as Alzheimer disease, cataracts, cellular immunity activation-related infections, autoimmune diseases, aids, cancers, depressions, tryptophan metabolic disorders or the like.

The invention discloses polysubstituted-indazole compounds as shown in a formula (I) which is described in the specification, a preparation method for the compounds, and application of the compounds as IDO inhibitors. The compounds provided by the invention can be used for preventing and / or treating a plurality of diseases, such as Alzheimer's disease, cataract, infections related to cellular immune activation, autoimmune diseases, AIDS, cancers, depression, the metabolic disorder of tryptophan or the like.

The invention belongs to the technical filed of medicinal chemistry and particularly relates to a medical application of a granaticin type compound. The compound is used for preventing or treating diseases, caused by IDO and / or TDO, with pathological characteristics related to tryptophan metabolism, wherein the diseases comprise but is not limited to tumor immune escape, or the virus infectious diseases, or the nervous system diseases, or the mental diseases or the cardiovascular diseases or the like.

The invention belongs to the technical field of medicines, and relates to medicinal and skin care applications of tryptophan metabolites comprising indole-3-formaldehyde (IAId) and the like, in particular to an application of tryptophan metabolites comprising indole-3-formaldehyde in preparing of medicines and skin care products with an immunoregulation effect. Experiments show that tryptophan metabolites such as IAId can inhibit AD-like inflammation and psoriasis-like inflammation induced by MC903 and inhibit infiltration of CD4+, Gr1+ positive cells in dermis, inhibit the expression of inflammatory factors, reduce the degree of skin percutaneous water loss, and inhibit scratching behavior in mice. Experimental results prove that tryptophan metabolites such as IAId have a clear anti-AD-like inflammation effect, and can be used for preparing drugs and skin care products for preventing and treating atopic dermatitis (eczema), especially for preparing an external preparation for preventing and treating acute and chronic inflammation caused by abnormal immune response. The invention provides a new drug choice for prevention and treatment of atopic dermatitis in the clinical test stageand clinical application, and has a wide commercial application prospect.

The invention discloses a 1H-indazole-4-ether compound, a preparation method thereof, and application of the 1H-indazole-4-ether compound serving as an IDO inhibitor. The 1H-indazole-4-ether compoundcan be used for preventing and / or treating various diseases such as Alzheimer's disease, cataract, infection related to cell immune activation, autoimmune disease, AIDS, cancer, depression or tryptophan metabolic disorder.

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)

The invention discloses a use of a naphthoquinone derivative as an inhibitor for IDO1 and / or TDO. The derivative is shown as a general formula (I), and the definition of each substituent is detailed in the specification. The compound represented by the general formula (I) has an inhibitory effect on indoleamine-2,3-dioxygenase 1 (IDO1) and / or tryptophan-2,3-dioxygenase (TDO), and can be used for treating diseases with IDO1- and / or TDO-mediated tryptophan metabolism as pathological features, including but not limited to tumors, autoimmune diseases, infectious diseases, Alzheimer's disease, depression, and anxiety disorder.

The invention discloses imidazole methylamine derivatives having the activity of an indoleamine-2, 3-dioxygenase (IDO) inhibitor, and a synthesis method of the imidazole methylamine derivatives. The invention in particular relates to the indoleamine-2, 3-dioxygenase (IDO) inhibitor with a novel structure, and application of the inhibitor in pharmacy, belonging to the field of compound medicines. The compounds provided by the invention are as shown in a formula I, have the novel structure, show the good IDO inhibitory activity, provide a new option for clinical treatment of diseases associatedwith abnormal IDO activity, and provide a potential medicine for prevention and / or treatment of diseases such as Alzheimer disease, cataracts, cellular immune activation-related infections, autoimmunediseases, AIDS, cancers, depression or abnormal metabolism of tryptophan.

The invention discloses a method for preparing a DL-tryptophan feed additive. The method comprises the following steps: (1) cultivating a high-yield strain of L-tryptophan; (2) placing the high-yield stable strain into a culture medium, and performing large-scale fermentation culture under set fermentation culture process conditions to obtain an L-tryptophan fermentation culture liquid; (3) extracting L-tryptophan; (4) preparing L-tryptophan mixed feed. The mutation spectrum is designed according to the metabolic pathway of tryptophan, mutation screening is performed by different mutagens, the strain with the L-tryptophan production amount being 39.16 g / L is obtained, and the L-tryptophan fermentation culture liquid is applied to the feed additive. The L-tryptophan feed additive produced in the liquid state has the advantages of low cost, safe quality and high animal absorption and utilization rate, can improve balance of amino acid in livestock and poultry animal feed and increases the feed utilization and protein synthesis.

The present invention relates to an N-benzyl tryptanthrin derivative, and preparation method and use thereof. The N-benzyl tryptanthrin derivative of the present invention is characterized in that the derivative has a structural general formula as represented by formula 1, wherein each group is defined as in the specification. The preparation method of the compound is simple, has mild conditions and high yield, and is suitable for industrial production. The N-benzyl tryptanthrin derivative has good indoleamine-2,3-dioxy-genase (IDO) inhibitory activity, and can be used for treating diseases having the pathological feature of IDO-mediated tryptophan metabolism.

The invention discloses a liver cancer prognosis evaluation method based on tryptophan metabolism genes. The method comprises the following steps: calculating a risk index of a liver cancer patient based on a formula (1); dividing a RiskScore high-risk group and a RiskScore low-risk group according to a threshold value '0', drawing a survival curve by adopting a Kaplan-Meier method, and evaluating the prognosis effect of the liver cancer; the liver cancer clinical prognosis evaluation model has the advantages that the liver cancer clinical prognosis evaluation model is constructed according to the 10 key genes of the tryptophan metabolic phenotype, and the model has high robustness, is independent of clinical pathological characteristics, can independently evaluate the prognosis condition of a liver cancer treatment means, and provides a foundation for effective analysis of treatment data. And data support is provided for optimizing a liver cancer clinical treatment scheme and formulating a personalized treatment scheme.

The invention discloses an acute pancreatitis diagnosis model based on tryptophan metabolites and application, and belongs to the technical field of biological detection. The acute pancreatitis diagnosis model comprises three tryptophan metabolites: DL-Tryptophan, Indole-3-acrylic acid and Indole-3-lactic acid, and the acute pancreatitis is determined by detecting the content change of the three tryptophan metabolites in the serum. The tryptophan metabolite composition can be used as the acute pancreatitis diagnosis model, and the acute pancreatitis diagnosis model has the acute pancreatitis diagnosis sensitivity of 100%, the acute pancreatitis diagnosis specificity of 75%, the acute pancreatitis diagnosis false positive rate of 25% and the acute pancreatitis diagnosis false negative rate of 0%.

The invention discloses an L-tryptophan producing bacterial strain, a gene engineering construction method for the L-tryptophan producing bacterial strain and a method for producing and preparing L-tryptophan by a fermentation method. Genes relevant to an L-tryptophan metabolic pathway are mutated and deleted by the gene engineering measure to promote metabolism disorder of the L-tryptophan, so that the L-tryptophan has high yield; simultaneously, the metabolic flow of the L-tryptophan is reinforced by gene integration or by overexpressing the genes relevant to the L-tryptophan metabolic pathway through a proper expression vector; finally, a large quantity of L-tryptophan can be accumulated in the fermentation solution by fermenting.

The invention discloses 1H-indazole-4-amine compounds and further discloses a preparation method of the 1H-indazole-4-amine compounds and an application of the 1H-indazole-4-amine compounds as an IDO (indoleamine 2,3-dioxygenase) inhibitor. The 1H-indazole-4-amine compounds can be used for preventing and / or treating various diseases such as Alzheimer's disease, cataract, cellular immune activation associated infection, autoimmune disease, acquired immune deficiency syndrome, cancer, depression or tryptophan metabolic disorder.