52 results about "TLR8" patented technology

The invention relates to the technical field of medicines, in particular to a polypeptide coupling medicine of a somatostatin receptor binding peptide coupling TLR agonist and a preparation method of the polypeptide coupling medicine. The polypeptide coupling medicine of the somatostatin receptor binding peptide coupling TLR agonist provided by the invention comprises at least one compound in a formula I-1 and a formula I-2 in the specification or a pharmaceutically acceptable salt of the compound. According to the polypeptide coupling drug based on the specific molecular structure provided by the invention, somatostatin receptor binding peptide is coupled with a TLR agonist, so that the polypeptide coupling drug not only has tumor tissue targeting property, but also can activate TLR7 and TLR8 receptors on cytoplasm endosomes in tumor tissues, exerts an anti-tumor immunostimulation effect, and has a good application prospect. Meanwhile, the immunotoxicity of blood and non-specific organs is lower.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a TLR8 inhibitor in preparation of a medicine for treating systemic sclerosis. The invention has the following advantages: the compound shown in the formula (I) and / or the pharmaceutically acceptable salt, the deuterated substance, the solvate and the precursor of the compound have obvious improvement on skin lesion of patients with systemic sclerosis. The invention provides application of the compound shown in the formula (I) and / or the pharmaceutically acceptable salt, the deuterated compound, the solvate and the precursor of the compound in preparation of drugs for treating systemic sclerosis, and is expected to provide a new strategy for treatment of systemic sclerosis. # imgabs0 # (I)

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 discloses an antibody-drug conjugate and a preparation method and application thereof, in particular, a conjugate of an anti-PD-L1 antibody and a TLR7 and / or TLR8 agonist and a pharmaceutical composition, preparation method and application thereof. The present invention obtains a modified anti-PD-L1 antibody with a mutant cysteine ​​by gene editing, which basically retains the structure of the original antibody and can be used for the construction of an antibody-drug conjugate. Through anti-tumor experiments, it was found that the obtained antibody-drug conjugate has better activity, such as strong anti-tumor activity, can significantly improve the survival rate of tumor-bearing animals, and has significantly reduced toxicity, less burden on the body of experimental animals, greatly reduces the minimum effective dose of small molecule drugs when used alone, expands its therapeutic window, and is expected to be used in the development of therapeutic drugs for various diseases (such as tumors, viral diseases such as hepatitis B, etc.), with good application prospects and value.

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).

The present application relates to a compound of formula (I) for inhibiting Toll-like receptor 8 (TLR8) activity, a stereoisomer thereof, an atropisomer thereof, a deuterated derivative thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the atropisomer thereof or a pharmaceutically acceptable salt of the deuterated derivative thereof, and a method for preparing the compound, a composition thereof and the use thereof.

The present invention relates to oligonucleotides that inhibit Toll-like receptor 7 (TLR7) and / or Toll-like receptor 8 (TLR8) or enhance TLR8 and uses thereof.

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 present disclosure provides circular polyribonucleotides including a sequence including: a circularization element; a first spacer; an internal ribosome entry site (IRES) sequence; a sequence encoding a polypeptide; and a second spacer, where the sequence encoding the polypeptide has been codon-optimized to reduce the number of uracil ribonucleotides and / or reduce or remove TLR7- and TLR8-recognition motifs, and kits and compositions thereof. The present disclosure also provides methods of treating subjects in need thereof with the circular polyribonucleotides and compositions described herein.

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 relates to compounds of formula (I):or a salt or solvate thereof, wherein the variables are as described herein. Compounds of formula (I) and pharmaceutical compositions thereof are antagonists of toll-like receptors such as TLR7, TLR8 and / or TLR9 that are useful for inhibiting immune response and treating diseases associated with undesirable immune response.

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 present technology is directed to TLR7 and TLR8 agonist compounds, compositions, and methods of using the same for the treatment of cancers and as vaccine adjuvants.

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.

The present disclosure relates to methods of selecting, designing or modifying oligonucleotides so that they inhibit cyclic GMP-AMP synthase (cGAS), Toll-Like Receptor 3 (TLR3) Toll-Like Receptor 7 (TLR7), Toll-Like Receptor 8 (TLR8) and / or 5 Toll-Like Receptor 9 (TLR9), or potentiate Toll-Like Receptor 8 (TLR8). Additionally, the present disclosure resides in methods of selecting, designing or modifying oligonucleotides such that they exhibit reduced cGAS inhibitory activity.

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 invention provides novel imidazoquinoline amine derivatives, having agonistic activities to Toll-like receptors (TLRs), in particular TLR7 and / or TLR8, pharmaceutical compositions thereof, and methods of treatment, reduction or prevention of 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.

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.

A pyrimidine derivative represented by formula (I-1), formula (I-2), formula (II-1) or formula (II-2), or a stereoisomer, tautomer, isotope derivative, hydrate, solvate, prodrug, and pharmaceutically acceptable salt thereof. The pyrimidine derivative can be used as an effective TLR7 and / or TLR8 agonist, and has the characteristics of good selectivity, high activity, and good safety. Also provided are a preparation method for the pyrimidine derivative and a pharmaceutical composition thereof. The compound or the pharmaceutical composition thereof can be used for preparing drugs for preventing or treating the following diseases: infectious diseases, respiratory system diseases, immune-related diseases, viral diseases or tumors.

The invention provides alkyne compounds, stereoisomers, tautomers or pharmaceutically acceptable salts thereof, and also provides methods related to preparation and application of the compounds, pharmaceutical compositions containing the compounds and related methods for regulating immune system diseases. According to the present invention, the compound having the alkyne structure shows the excellent immune system disease regulation effect, and has wide application prospects in the immune system disease regulation treatment field.

A compound of formula I, and a preparation method therefor and a use thereof as a TLR7 and / or TLR8 agonist are provided. The compound can be used for preparing a pharmaceutical composition for treating or preventing tumors or infections caused by viruses.

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