183 results about "Activating receptors" patented technology

The invention discloses a polypeptide or a pharmaceutically acceptable salt thereof. The polypeptide has an amino acid sequence as shown in SEQ ID NO: 1 or an amino acid sequence in a conservative modification form thereof. The polypeptide or the pharmaceutically acceptable salt thereof disclosed by the invention can be combined with GLP1R and is used for effectively activating the GLP1R. The GLP1R activating polypeptide is obtained through precise calculation and deep learning model optimization, has a short sequence, has unique amino acid arrangement compared with a traditional GLP-1 analogue, can effectively activate a GLP1R receptor, can also be used for treating or preventing metabolic disorder related diseases, and has a good application prospect. For example, obesity, diabetes, dyslipidemia related diseases, fatty liver diseases, metabolic syndromes, non-alcoholic fatty liver diseases and the like.

The present invention provides a method for inducing fat accumulation in a cell of a fish, including contacting a cell obtained or derived from a fish with an effective amount of a composition including: (i) a fat accumulation inducing agent; and (ii) a carrier, wherein the fat accumulation inducing agent consists essentially of a free fatty acid and a peroxisome proliferator-activated receptor gamma (PPARy) agonist. Further provided are a cultured fish cell including an increased amount of a PUFA and a reduced amount of MUFA, compared to a control fish cell, and an edible composition including the same.

The invention discloses a piperidine ring compound as well as a synthesis method, pharmaceutically acceptable salt and application thereof, and belongs to the technical field of medicines, and the piperidine ring compound shows that the piperidine ring compound has a transcription enhancing effect on a fatty acid beta-oxidation key gene-CPT1 alpha at the downstream of a peroxisome proliferator-activated receptor alpha (PPAR alpha), and can be used for preparing a medicine for preventing and treating the fatty acid beta-oxidation key gene-CPT1 alpha. The compound is expected to be used as a potential medicine for treating the non-alcoholic fatty liver disease.

This invention belongs to the field of biomedical technology and discloses a method for targeting GABA. A The receptor-dependent cyclic peptide analgesic DZ2 has the following amino acid sequence: Cys-Asn-Thr-Glu-Arg-Pro-Gly-Met-Leu-Asp-Phe-Lys-Gly-Lys-Ala-Lys-Trp-Asp-Ala-Trp-Cys, where the N-terminal Cys and C-terminal Cys are cyclically linked by a disulfide bond, and the molecular weight is 2454.81 g / mol. This cyclic peptide can be obtained through classic Fmoc-solid-phase synthesis, using GABA... A Receptor-targeting drugs play an important role in drug development. The compounds provided in this invention can activate GABA. A The receptor generates a GABA-like inward current. Furthermore, DZ2 exhibits excellent analgesic effects in a mouse pain model, providing a potential alternative for GABA-based analgesics. A This provides new ideas and theoretical basis for the development of receptor-based analgesics.

The invention relates to the field of biological medicines, in particular to a chimeric cytokine activated receptor for activating lymphocytes by using soluble immunosuppressive molecules and application of the chimeric cytokine activated receptor in tumor treatment. The chimeric cytokine activation receptor and a chimeric antigen receptor for recognizing tumor antigens are connected in parallel to form a co-expressed polycistron structure. Wherein the chimeric cytokine activation receptor comprises an scFv structural domain, a transmembrane structural domain and a cytokine chimeric activation structural domain which specifically recognize and bind soluble immunosuppressive molecules. The CAR-NK cell can specifically recognize soluble inhibitory factors in the tumor microenvironment and improve the in-vivo and in-vitro anti-tumor efficacy of the CAR-NK cell, and can be used for treating solid malignant tumors.

Described herein are fusion proteins comprising an extracellular domain of an immune checkpoint receptor and a cytoplasmic domain of an activating receptor. Also described herein are fusion proteins comprising a cytoplasmic domain of an immune checkpoint receptor and an extracellular domain of an activating receptor. The present disclosure further provides methods of use of such fusion proteins.

The invention relates to tumor-targeted trimeric polypeptides based on the homotrimerization region from collagen XV or XVIII and which contain domains capable of specifically binding to and activating receptors of the TNFR family of costimulatory receptors as well as to the uses thereof in the treatment of cancer.

The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

Described herein are method of using fusion proteins composed of elements such as one or more proteins / polypeptides capable of translocating into an endoplasmic reticulum (ER) and an interleukin 18 (IL-18) or a fragment or variant of IL-18. The proteins / polypeptides capable of translocating into the ER include but are not limited to an immunoglobular protein such as Fc region, VHH antibody, and scFv, and a globular protein such as serum albumin. The IL-18 may be a precursor IL-18 that resembles the natural pro-cytokine in which IL-18 is fused to the C-terminus of its propeptide or a propeptide variant. These fusion proteins can be used in methods of treating cancer or fibrosis by activating an IL-18 receptor complex (RC) signal on a cell, releasing or exposing mature IL-18 in a tumor microenvironment or adjacent to a tumor and / or increasing memory CD8+ T cell proliferation.

The present application relates to single-domain antibodies and constructs comprising the single-domain antibodies, both of which exhibit affinity and specificity toward the CD16a activating receptor on natural killer cells and antigens on cancer cells, bacteria, parasites, or viruses.

Provided are a method and system for predicting an activation potency of agonist molecules on G Protein-Coupled Receptors (GPCRs). The method includes: blindly speculating complex structures formed by binding of a ligand to an activated receptor structure and an inactivated receptor structure, respectively, via global molecular docking; extracting an initial path enabling an inactivated complex structure to be activated to an activated complex structure based on an enhanced sampling algorithm; searching for a minimum free energy path closest to the initial path by applying an automatic path optimization algorithm; calculating a free energy distribution curve along the minimum free energy path by employing umbrella sampling and determining an energy barrier height and a free energy difference before and after activation, thereby determining the activation potency of the ligand structure on the GPCRs.

Provided is a fusion protein, which binds to ACTRII, also can activate a GLP1 receptor and / or an FGF21 receptor, and has better muscle-building and fat-reducing effects in a weight-reducing use.

The invention relates to the use of at least one phytoecdysone and / or at least one semi-synthetic derivative of 20-hydroxyecdysone, and at least one active ingredient having the capacity to activate the GLP-1 receptor, in the treatment of obesity, sarcopenic obesity or overweight in mammals. Figure for abstract: Fig. 1

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, in which the blocking receptor provides a signal that dominates a signal from the activating receptor.

The invention relates to the field of antibodies, in particular to a monoclonal antibody for treating overactive bladder and application of the monoclonal antibody. The monoclonal antibody specifically recognizes and is combined with an adrenergic receptor beta3 (ADR beta3), the monoclonal antibody is obtained through a hybridoma technology, and the M13 monoclonal antibody with high affinity is successfully screened out. The M13 antibody promotes the increase of cAMP concentration in smooth muscle cells and activates a PKA pathway by activating an ADR beta3 receptor, thereby promoting the relaxation of bladder smooth muscles, increasing the bladder capacity and reducing the non-autonomous contraction of detrusor muscles. Animal experiments prove that the M13 monoclonal antibody can effectively improve the urination frequency and urine volume of a mouse OAB model, and has a good clinical application prospect. The monoclonal antibody and the preparation method thereof can be widely applied to the field of treatment of overactive bladder.

The invention provides application of 4-deoxy-4-arylthio-N-pyranoside compounds, the compounds have the agonistic activity of peroxisome proliferator activated receptors (PPAR) alpha and gamma, and nine compounds have the agonistic activity on the PPAR alpha by participating in expression of related genes such as glycometabolism, lipid metabolism and inflammatory reaction; 11 compounds have agonistic activity on PPAR (peroxisome proliferator activated receptor) gamma; the eight compounds have the activity of double excitation of PPAR alpha and PPAR gamma. The compound can be used for preventing and treating type 2 diabetes mellitus, hyperlipidemia, non-alcoholic hepatitis and neurodegenerative diseases, and has an important application prospect.

Formula I: A compound or its derivative, or its salt or prodrug, having the structure of TIFF2025524142000026.tif2292, wherein m = 2 and n is an odd number between 4 and 20, and Formula II: Disclosed is a compound or its derivative, or its salt or prodrug, having the structure of TIFF2025524142000027.tif2696, wherein m and n are independently integers between 2 and 20. Also provided are compositions and methods of using the compounds for the therapeutic modulation of peroxisome proliferator-activated receptor (PPAR).

The present invention relates to a nucleic acid molecule encoding a multispecific antigen-binding protein and exhibiting significantly improved expression efficiency in vivo. In the multispecific antigen-binding protein of the present invention, specifically, a bispecific antibody that recognizes a tumor antigen or a viral antigen and a natural killer cell-specific activating receptor, the light chain variable region (VL) and the heavy chain variable region (VH) of a receptor-recognizing site of a natural killer cell-specific activating receptor are sequentially arranged in the N-terminus to the C-terminus direction, thereby increasing expression efficiency by up to 8-fold. Therefore, the present invention provides an optimal mRNA structure capable of most efficiently expressing bispecific antibodies in vitro and in vivo, thereby enabling effective use thereof for not only mass-production of recombinant bispecific antibodies but also as an excellent mRNA therapeutic agent for stable and continuous production of a therapeutically effective amount of bispecific antibodies in the body of a patient.

Benzyl derivative compounds having peroxisome proliferator-activated receptor alpha (PPARα) agonist activity, kits and compositions containing such compounds, and methods of using them to enhance PPARα activity to treat diseases and / or conditions involving inflammation and / or angiogenesis, particularly diseases and / or conditions of the eye such as, but not limited to, retinal inflammation, retinal neovascularization, retinal vascular leakage, retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and diabetic macular edema.

Provided are methods of treating subjects in need of an anti-fibroblast growth factor receptor 4 (anti-FGFR4) therapy. The methods comprise administering to the subjects a therapeutically effective amount of a peroxisome proliferator-activated receptor (PPAR) alpha agonist in combination with the anti-FGFR4 therapy. The methods can comprise administering to the subject a therapeutically effective amount of PPAR alpha agonist and a bile acid sequestrant. Also provided are compositions comprising an FGFR4 inhibitor, a PPAR alpha agonist, and, optionally, a bile acid sequestrant. The methods attenuate the dysregulation of bile acid biosynthesis caused by FGFR4 inhibition with anti-FGFR4 therapies. The methods reduce the severity and / or incidence of adverse events associated with anti-FGFR4 therapies.

The present invention relates to a personal care composition. Particularly, the present invention relates to a use of a combination of a sugar alcohol and a polyalkylene glycol, as a prebiotic in a personal care composition comprising one or more activators of peroxisome proliferator-activated receptors, for protecting skin against harmful microorganisms and for providing skin brightening.

The invention provides application of CAR-NK (chimeric antigen receptor-natural killer) cells in preparation of drugs for treating autoimmune diseases, and the CAR-NK cells express a chimeric antigen receptor and a fusion protein of a targeted NKG2D ligand; the fusion protein comprises an IL-15R alpha and an IL-15, and the IL-15 and the IL-15R alpha are connected with each other. According to the CAR-NK cell disclosed by the invention, the specific recognition of MICA / B molecules on the surface of an over-activated T / B cell of an SLE patient is realized by highly expressing an NKG2D activated receptor, and the durability of an intracellular signal is enhanced so as to resist cell depletion; meanwhile, the super IL-15 fusion protein is expressed to prolong the in-vivo survival and function duration time, and the effect of treating the SLE is improved through the cooperation of the dual mechanisms.

Provided herein are fusion proteins comprising a peroxisome proliferator-activated receptor delta (PPAR-5) sequence linked to an activation domain sequence for increasing immune cell activity against cancer cells and also provided herein are CPT1A proteins for increasing immune cell activity against cancer cells.

Benzyl derivative compounds having peroxisome proliferator-activated receptor α (PPARα) agonistic activity, kits and compositions containing such compounds, and methods of their use in enhancing PPARα activity for treating diseases and / or conditions involving inflammation and / or angiogenesis, particularly ocular diseases and / or conditions such as but not limited to retinal inflammation, retinal neovascularization, retinal vascular leakage, retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and diabetic macular edema.

The invention discloses a construction method of a spontaneous lupus adipositis animal model, which comprises the following steps: constructing keratinocytes with genotypes of PPAR [gamma] flox / flox- / -Krt5-CreERT < 2 + > / -Adipoq-Cre < + > / -and PPAR [gamma] flox / flox- / -Krt5-CreERT < 2 + > / -Adipoq-CreERT < 2 + > / -and fat cells into a conditional PPAR [gamma]-active receptor gamma gene knockout mouse, so as to construct the animal model with the spontaneous lupus adipositis animal model. Then knocking out PPAR gamma genes in keratinocytes and adipocytes by using a gene knockout activator, so that the mice spontaneously have the phenotypes of lupus septicaemia, including local skin unhairing, lipoatrophy, persistent skin lesion, proteinuria and serum autoantibodies; histological examination finds that lobular adipositis, glomerular volume increase, mesangial cell hyperplasia, inflammatory cell infiltration, glomerular IgG deposition and the like are mainly caused by dermal immune cell infiltration and subcutaneous fat layer lymphocyte infiltration, clinical symptoms of patients with lupus adipositis are simulated, and an important tool is provided for related research of lupus adipositis.

PLXDC1 and PLXDC2 represent a new cell-surface receptor family (collectively referred to as PLXDC proteins). The present disclosure reports that Domain A of the PLXDC proteins functions as an inhibitory domain, as the deletion thereof activates PLXDC signaling. Antibodies and antigen-binding fragments that bind to Domain A can therefore relieve its inhibitory function and activate PLXDC signaling, leading to killing of endothelial cells in pathogenic blood vessel that express the PLXDC protein. Methods are described for efficient screening of PLXDC-activating antibodies that bind to Domain A. In particular, the method entails the use of a small molecule agent that binds the PLXDC protein, making Domain A more accessible to a test antibody. With the new method, antibodies that bind to Domain A and can activate PLXDC signaling have been successfully identified. These antibodies, as well as their antigen-binding fragments, are useful for treating diseases characterized with PLXDC-expressing pathogenic blood vessels.

The invention relates to the technical field of medicines, in particular to application of a growth hormone releasing peptide Ghrelin receptor in itching intervention. By adjusting the activity of the receptor, the invention provides a new strategy for intervening pruritus: activation of the Ghrelin receptor can be used for inducing pruritus so as to construct a disease model; and inhibiting the Ghrelin receptor is used for preventing or treating pruritus, and the pruritus comprises acute pruritus and chronic pruritus. In specific implementation, the inhibition of the receptor is realized by applying the Ghrelin receptor antagonist, and the activation of the receptor is realized by applying the Ghrelin receptor agonist. Therefore, by targeting the Ghrelin receptor, controllable induction and efficient inhibition of pruritus are realized, mechanism innovation, treatment practicability and conversion feasibility are integrated, and a breakthrough strategy is provided for prevention and treatment of pruritus-related diseases.

The application relates to cytokine receptor agonists comprising: i) a first PD-1 binding domain capable of binding a first epitope on PD-1, ii) a second PD-1 binding domain capable of binding a second epitope on PD-1, iii) an IL2Rγ binding domain, iv) an IL2Rβ binding domain, and v) an Fc region, and wherein the first and second PD-1 binding domains do not compete for binding on PD-1. The PD1-binding domains simultaneously bind the PD-1 and the IL-2 receptor-binding domains bind subunits of an IL-2 receptor complex. Biparatopic assembly of the IL-2 receptor-binding domains in the presence of PD-1 allows to selectively activate IL-2 receptors and effectively mimic cytokine activity in a targeted manner.