34 results about "TLR8" patented technology

The present invention relates to a novel purine derivative compound and a composition for enhancing an immune response comprising same as an active ingredient. The compound of the present invention not only has a nanomolar EC50 value for TLR7, which is an intracellular membrane receptor of immune cells, but also has high selectivity for TLR7 compared to TLR8, which has a similar structure and is mainly distributed in the endoplasmic reticulum (ER), thereby being able to induce sustained immune activation. Therefore, the compound of the present invention can be effectively used as an efficient vaccine adjuvant composition against various RNA viruses including influenza virus, SARS-CoV-2, and hepatitis C virus.

What is described is a peptide for use in the reduction of side-effects in form of immunostimulatory reactions / effects which occur with gene therapy, wherein the peptide is coupled to a nucleic acid molecule used in gene therapy. Furthermore, such a peptide is described for use in the reduction of side-effects in form of immunostimulatory reactions / effects which occur with gene therapy, wherein the peptide is coupled to a nucleic acid molecule used in gene therapy, wherein the immunostimulatory reactions / effects are induced by activation of IFIT1 / 2, IRF9, TLR3, TLR7, TLR8 or PKR.

The present invention provides novel drug-linker conjugates and antibody-drug conjugates of imidazo quinoline amine derivatives, which have agonistic activity against Toll-like receptors (TLRs), in particular TLR7 and / or TLR8, also provided are pharmaceutical compositions and methods of treatment against certain diseases or conditions mediated by or associated with TLR7 and / or TLR8 (e.g., graft rejection, autoimmunity, inflammation, allergy, asthma, infection, sepsis, cancer, and immunodeficiency).

A Toll-like receptor (TLR) is an indispensable component of an innate immune system and plays a key role in identifying and coping with microbial pathogens. TLR7, TLR8, and TLR9 are located in the endosome-lysosome compartment within the cell and then exclusively used to detect nucleic acids of a microorganism after the microorganism is swallowed and reaches the endosome compartment. The biological importance of the TLR agonists lies in that they can be used as powerful tools for studying innate immune responses, developing vaccines and potential therapeutic applications. In addition, TLR agonists have been explored for use as immunotherapy, while these TLR antagonists can be used as new pathogenic nodes in the context of different autoimmune diseases. Therefore, the agonists and antagonists of the endosomal TLR have therapeutic significance in different clinical backgrounds. The previous study on 8-oxo adenines shows that the C-6-site-NH2 group is extremely important for the recognition of agonistic active sites and the subsequent induction of interferon (IFN). The present invention explores the ability of a hydrogen-substituted 8-oxopurine derivative that does not contain an essential C-6 amine group. The C-6 amino group in the 8-oxopurine derivative is substituted by hydrogen (H), providing an exciting opinion for regulating the endosome TLRs (Toll-Like Receptors). The ability of 8-oxopurine derivatives to modulate the endosomal TLR has been reported, which derivatives are related / interrelated to various substitutions at N-7, N-9 and C-2, all derivatives containing hydrogen at C-6. Structure 1

The invention relates to a pyrimidino aromatic ring compound and application thereof in medicines, in particular to application of the pyrimidino aromatic ring compound as a TLR8 agonist. Specifically, the invention relates to a compound as shown in a general formula (I) or a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and application of the compound as a drug, especially application of the compound as a TLR8 agonist. Wherein the variables are defined in the specification.

This application relates to pyrimidine derivatives described in formula (I-1), formula (I-2), formula (II-1), or formula (II-2), or their stereoisomers, tautomers, isotopic derivatives, hydrates, solvates, prodrugs, and pharmaceutically acceptable salts, which can be used as effective TLR7 and / or TLR8 receptor agonists and are characterized by good selectivity, high activity, and excellent safety. This application also provides a method for preparing the pyrimidine derivatives and a pharmaceutical composition thereof. The compounds of this application or their pharmaceutical compositions can be used in the preparation of pharmaceuticals for the prevention or treatment of infectious diseases, respiratory diseases, immune-related diseases, viral diseases, or tumors. TIFF2026528992000173.tif3891

The invention relates to a pyrimidino aromatic ring compound and application thereof in medicines, in particular to application of the pyrimidino aromatic ring compound as a TLR8 agonist. Specifically, the invention relates to a compound as shown in a general formula (I) or a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and application of the compound as a drug, especially application of the compound as a TLR8 agonist. Wherein the variables are defined in the specification.

The invention provides a sika deer sperm sorting solution, a sika deer Y sperm sorting kit based on the sorting solution and application, and relates to the technical field of livestock breeding. The sika deer sperm sorting liquid comprises a sorting basic liquid and a Y sperm sorting functional component, wherein the Y sperm sorting functional component is prepared from rasimod and hyaluronic acid. Rescimod in the sika deer sperm sorting liquid I can be specifically combined with a sika deer X sperm TLR7 / TLR8 membrane receptor to inhibit the movement ability of the sika deer X sperm TLR7 / TLR8 membrane receptor, and a Y sperm is not affected due to lack of the receptor; on the basis, hyaluronic acid in the sorting liquid I and the sorting liquid II forms a physical barrier by increasing the viscosity of the sorting liquid, X sperms with limited movement and Y sperms with insufficient activity are effectively blocked, the Y sperms with high activity cross a barrier layer formed by the sorting liquid I and the sorting liquid II to enter a collecting liquid, then efficient sorting of the functional Y sperms of the sika deer is successfully achieved, and the sorting efficiency of the functional Y sperms of the sika deer is improved. The high-purity and high-activity Y sperms are enriched.

The invention provides a lipidoid Toll-like receptor agonist derivative as well as preparation and application thereof, and particularly provides a compound as shown in a formula I, a preparation method of the compound and application of the compound as a TLR7 and / or TLR8 agonist. The compounds can be used as immunostimulators and adjuvants.

This application relates generally to toll like receptor modulator compounds and pharmaceutical compositions which, among other things, modulate toll-like receptors (e.g. TLR8), and methods of making and using them.

Provided are conjugates that can be used for insitu cancer vaccination, such as for cancers with limited accessibility (e.g., lung cancer, pancreatic cancer, renal cancer, etc.) and metastatic disease in situations where the primary tumor has been surgically resected.SOLUTION: Provided are complexes comprising a knottin peptide comprising a modified loop that binds to a cell surface molecule and an immunostimulatory agent conjugated to the knottin peptide via a linker. In some embodiments, the immune stimulating agent activates a pathogen recognition receptor (PRR). For example, the immunostimulatory agent can be a toll-like receptor (TLR) agonist, e.g., an agonist of TLR7, TLR8, and / or TLR9. Also provided are compositions (e.g., pharmaceutical compositions) comprising the complexes of the disclosure, as well as kits comprising such compositions and methods of using such compositions, e.g., to treat an individual having cancer.SELECTED DRAWING: Figure 1

The invention relates to a pyrimidino aromatic ring compound and application thereof in medicines, in particular to application of the pyrimidino aromatic ring compound as a TLR8 agonist. Specifically, the invention relates to a compound as shown in a general formula (I) or a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and application of the compound as a drug, especially application of the compound as a TLR8 agonist. Wherein the variables are defined in the specification.

4-aminoimidazoquinoline compounds and their use are described. The compounds of the invention are dual agonists of Toll-like receptors 7 (TLR7) and TLR8, which induce the expression of IL-12 and IP-10 without over-inducing IL-6. These dual TLR7 / 8 agonists are potentially useful drugs as immune response modifiers. The use of a compound or a salt thereof, according to the invention, in the manufacture of a medicament for the treatment of a disease or condition in which activation of TLR7 and / or TLR8 provides a benefit in a subject in need is described. A compound or pharmaceutical composition for the treatment of a viral infection, cancer, and / or an allergic disease, or for the activation of effective immune responses against a viral infection, a tumor, and / or an allergic disease in a subject in need, is also described.

This invention provides a class of Toll-like receptor agonists, their preparation, and applications. Specifically, this invention provides a compound of Formula I, its preparation method, and its use as a TLR7 and / or TLR8 agonist. The compound can be used to prepare pharmaceutical compositions for treating or preventing tumors or viral infections.

The invention relates to a pyrimidino aromatic ring compound and application thereof in medicines, in particular to application of the pyrimidino aromatic ring compound as a TLR8 agonist. Specifically, the invention relates to a compound as shown in a general formula (I) or a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and application of the compound as a drug, especially application of the compound as a TLR8 agonist. Wherein the variables are defined in the specification.

The present invention pertains to a new method for the diagnosis, prognosis, stratification and / or monitoring of a therapy, of a pulmonary dysfunction in a subject. The method is based on the determination of the level of a panel of biomarkers selected from TM4SF18, TRGV9, ADORA2A, H963, IRF2, TNFSF14, TRIB1, SMAD3, TSLP, SLAMF8, THBS1, SOD1, HAS2, TLR2, THBD, TRA, TFEC, SPHK1, COL3A1, Elastin, IL6R, SN, TEK, SOX7, CXCL9, CXCL10, SLC38A6, SLC15A3, TGFA, SLPI, VWF, TLR8, TGFB1, CXCR6, CCL24, PD1, PLA1A, TRD, CTLA4, MMP9, CD301, PDL1, PDL2, TGFB1, CXCR6, CCL24, PD1, PLA1A, TRD, CTLA4, MMP9, and CD301. The new biomarker panels of this invention allow diagnosing and even stratifying various pulmonary dysfunctions in a subject, and even allow early detection of Chronic lung allograft dysfunction (CLAD). Furthermore provided are diagnostic kits for performing the methods of the invention.

The present invention discloses a benzazepine derivative, a conjugate containing the same, and applications thereof. The present invention provides an antibody-immunostimulatory conjugate represented by Formula I or a pharmaceutically acceptable salt thereof. The benzazepine derivative has a good regulatory effect on TLR8 and can effectively treat, alleviate, and / or prevent various related diseases caused by immunosuppression, such as cancer. [Formula 1] JPEG2025537044000630.jpg13169

This application relates to the field of chemical pharmaceutical technology, and more particularly to an imidazoquinoline compound having an alkylthio or alkyldithio group, its preparation method, and its application. The imidazoquinoline compound of this application includes the imidazoquinoline compound shown in Formula I and its pharmaceutically acceptable salt. This imidazoquinoline compound can activate TLR7 and TLR8 receptors, and after local injection, the level of the inflammatory factor IL6 in the blood is further reduced compared to the prototype molecule 78A1. While achieving local immunostimulation, it minimizes the non-specific immunotoxicity caused by cytokine storms, thus significantly improving safety. Therefore, the imidazoquinoline compound provided in this application can be used more safely for local immune activation, such as for tumor treatment or as an immunostimulatory adjuvant for vaccines.

The invention discloses a bovine TLR8 specific protein nano antibody and application thereof, and belongs to the technical field of nano antibodies. According to the preparation method disclosed by the invention, three bovine TLR8 specific protein nano antibodies, namely, Nb-TLR8-4, Nb-TLR8-5 and Nb-TLR8-6, are successfully prepared; the prepared three nano antibodies are strong in specificity, high in purity, good in functional integrity and excellent in biological activity and reactogenicity; the provided three nano antibodies have different thermal stability, and the activity of Nb-TLR8-4 is stable before 60 DEG C and then gradually decreases; the activity of the Nb-TLR8-5 is stable before 50 DEG C, and is sharply reduced after 50 DEG C; the activity of the Nb-TLR8-6 is relatively low on the whole and is continuously reduced along with temperature rise, so that the Nb-TLR8-6 can be applied to different temperature environments and is beneficial to screening of nano antibodies adaptive to specific temperature conditions.

The invention discloses application of a CSF2RA gene, an acute myelogenous leukemia marker, a prognosis effect analysis model and a construction method thereof, and relates to the technical field of biology. Mainly relates to application of a reagent for detecting the expression quantity of a CSF2RA gene or a Hub gene related to the CSF2RA gene in preparation of a product for predicting the prognosis effect of acute myelogenous leukemia. Meanwhile, the invention also discloses an acute myelogenous leukemia marker which is one or more of CD4, ITGAM, TLR4, TLR2, FCGR3A, IL10, CD86, TLR8, ITGAX and FCGR2B genes. The invention provides a new target CSF2RA for predicting the prognosis effect of the acute myelogenous leukemia, and provides a prognosis effect analysis model, and the result shows that the high expression of the CSF2RA gene or the Hub gene related to the CSF2RA gene is related to the poor prognosis of a patient with the acute myelogenous leukemia.

The invention relates to the field of medicinal chemistry, and particularly discloses a novel TLR8 agonist intermediate as well as a preparation method and application thereof, which are suitable for process development of 4, 6-diaminopyridino [3, 2-d] pyrimidine TLR8 agonists. According to the preparation method, tert-butyl is adopted to replace 2, 4-dimethoxybenzyl to serve as an amino protecting group, so that the crystallization property of the intermediate is remarkably improved, column chromatography is avoided, the cost is reduced, and the process stability is improved. The preparation method of the TLR8 agonist intermediate comprises the steps of reduction, acylating chlorination, coupling, amination and the like, has the advantages of being easy and convenient to operate, high in yield, environmentally friendly and the like, and is particularly suitable for industrial production.

The invention relates to a pyrimidino aromatic ring compound and application thereof in medicines, in particular to application of the pyrimidino aromatic ring compound as a TLR8 agonist. Specifically, the invention relates to a compound as shown in a general formula (I) or a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and application of the compound as a drug, especially application of the compound as a TLR8 agonist. Wherein the variables are defined in the specification.

This invention provides a probe library and kit for detecting genetic risk gene mutations in viral infections, belonging to the field of gene detection technology. The probe library and kit designed in this invention achieve, for the first time, the simultaneous detection of all mutations in the following 51 genetic risk genes for viral infections: CARMIL2, CCL2, CD27, CD70, CIB1, CTPS1, CXCR4, CYBC1(C17orf62), DBR1, FCGR3A, FCHO1, ICAM1, IFIH1, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IL10, IL10RA, IL10RB, IL... The probe library and kit of this invention contain 18BP, IRF3, IRF7, IRF9, MAGT1, LIG1, MCM2, NOS2, OAS1, POLR3A, POLR3C, POLR3F, PRKCD, RASGRP1, SH2D1A, STAT1, STAT2, TBK1, TICAM1, TLR3, TLR7, TLR8, TMC6, TMC8, TNFRSF9, TRAF1, TRAF2, TRAF3, TYK2, UNC93B1, and XIAP. This invention's probe library and kit can be used for detecting genetic variations in the risk of viral infection in clinical settings, assessing an individual's genetic risk of viral infection, and has broad application prospects.

The invention relates to a method of predicting an outcome of a breast cancer subject, comprising determining or receiving the result of a determination of a gene expression profile comprising the expression levels of four or more genes selected from a first, a second and / or a third gene expression profile, wherein the first gene expression profile comprising one or more immune defense response genes selected from the group consisting of: AIM2, APOBEC3A, CIAO1, DDX58, DHX9, IFI16, IFIH1, IFIT1, IFIT3, LRRFIP1, MYD88, OAS1, TLR8, and ZBP1, and / or the second gene expression profile comprising one or more T-Cell receptor signalling genes selected from the group consisting of: CD2, CD247, CD28, CD3E, CD3G, CD4, CSK, EZR, FYN, LAT, LCK, PAG1, PDE4D, PRKACA, PRKACB, PTPRC, and ZAP70, and / or the third gene expression profile comprising one or more PDE4D7 correlated genes selected from the group consisting of: ABCC5, CUX2, KIAA1549, PDE4D, RAP1GAP2, SLC39A11, TDRD1, and VWA2, said gene expression profile being determined in a biological sample obtained from the subject, determining the prediction of the outcome based on the gene expression profile comprising the expression levels of the four or more genes, wherein said prediction is a favourable risk or a non-favourable risk of breast-cancer related death, loco-regional recurrence and / or distant recurrence.

The present invention relates to oligonucleotides that maintain a Toll-Like Receptor 7 (TLR7) response and / or which potentiate Toll-Like Receptor 8 (TLR8) sensing.

Toll-like receptors (TLRs) are integral components of the innate immune system, serving as key players in the recognition and response to microbial pathogens. TLR7, TLR8 and TLR9 are located inside the cell within the endosomal-lysosomal compartments, subsequently specialized for detecting microbial nucleic acids after microbes get phagocytosed and reach the endosomal compartments. The biological importance of TLR agonists lies in their ability to serve as powerful tools for studying innate immune responses, developing vaccines, and potential therapeutic applications. Additionally, TLR agonists have been explored as immunotherapies, whereas antagonists of these TLRs could serve as novel pathogenic node in different autoimmune disease contexts. Thus, both agonists and antagonists of these endosomal TLRs have therapeutic significance in different clinical context. The previous studies in 8-oxoadenine class depicted that the C-6 position -NH2 group is extremely important for recognition of the agonistic active site and subsequent interferon (IFN) induction. The present invention explores ability of 8-oxopurine derivatives, which does not contain the essential C-6 amine group and was replaced with hydrogen. The replacement of C-6 amino with a hydrogen (H) in 8-oxopurine derivatives provided exciting insight into these endosomal TLR modulation. The ability to modulate the endosomal TLRs by 8- oxopurine derivatives in correlation / interrelation with various substitution at N-7, N-9 and C-2 with all the derivatives containing hydrogen at C-6 were reported.

The present invention relates to an antagonistic small molecule compound having a function of inhibiting an endosome toll-like receptor (TLR), and more particularly to: a small molecule compound for inhibiting a TLR3 / 7 / 8 / 9 signaling pathway; a composition for inhibiting a toll-like receptor comprising the small molecule compound; and a composition for preventing or treating an autoimmune disease, an inflammatory disease, or a viral disease. The compound according to the present invention shows very significant results in a systemic lupus erythematosus animal model, which not only prevents TNF-α secretion induced by poly I:C (TLR3 agonist), imiquimod (TLR7 agonist), TL8-506 (TLR8 agonist), or ODN2395 (TLR9 agonist), but also inhibits the production of inflammatory cytokines. This indicates that the compound can also be used for preventing or treating TLR3, TLR7, TLR8, or TLR9-related autoimmune diseases, inflammatory diseases, and viral diseases.

The application discloses application of TLR8 in preparation of ulcerative colitis diagnosis and treatment products, and belongs to the technical field of biological medicine. The application provides application of TLR8 in preparation of ulcerative colitis diagnosis products, the diagnosis products are used for detecting the expression level of TLR8 in peripheral blood samples, and the diagnosis products comprise detection reagents, detection kits and detection chips. Meanwhile, the application provides application of TLR8 in preparation and / or screening of ulcerative colitis treatment drugs, and application of a TLR8 inhibitor in preparation of ulcerative colitis treatment or alleviation drugs. The drugs can inhibit the expression of TLR8, reduce the phosphorylation level of p65 in the NF-kappa B channel, and then alleviate intestinal inflammatory reactions. The application clarifies the correlation between TLR8 and ulcerative colitis, provides a new target and detection means for early diagnosis of ulcerative colitis, simultaneously provides a new thought and a drug research and development direction for treatment of the disease, and has important clinical application value and industrialization prospects.

Disclosed are an imidazo[2,1-f][1,2,4]triazin-4-amine derivative used as a TLR8 agonist or a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing same. Further disclosed is a method for treating cancers using the imidazo[2,1-f][1,2,4]triazin-4-amine derivative or the stereoisomer thereof or the pharmaceutically acceptable salt thereof as a TLR8 agonist.