72 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.

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.

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.

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.

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.

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.

V1a RECEPTOR PARTIAL AGONISTS AND METHODS OF USE SOLUTION: The present invention provides novel partial V1a agonists for partial activation of V1a receptors. The partial V1a agonists have therapeutic indices of at least 20 (e.g., at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100). Also provided is a method of treating liver fibrosis, hepatocirrhosis, portal hypertension, peritoneal fluid, esophageal varices, fundic varices, hemorrhage, arterial hypotension, and / or hepatorenal syndrome, comprising administering to a subject in need thereof a therapeutically effective dose of a composition comprising one or more of the disclosed partial V1a agonists, optionally in combination with a V2 antagonist.SELECTED DRAWING: None

The present disclosure relates to a method for diagnosing and treating multiple-system atrophy (MSA) in a subject, the method comprising: determining in a subject-derived biological sample an expression level of a gene from the group consisting of: QKI, GGCX, MOCS1, NF1, LINC01572, PRRG3, HMBOX1, PLP1, PPP1CA, C8orf88, TGFB2, MASP1, TIAM1, SYNGAP1, ACTN1, EMP1, NFIL3, GPNMB, PGAM2, ST5, STON1, RFTN1, and MMP14; comparing the subject-derived expression level of the gene with a normal control expression level of the gene obtained from a non-neurodegenerative biological sample; diagnosing the subject as a having MSA by detecting a differential expression of the gene in the subject-derived biological sample as compared to the normal control expression level; and administering a peroxisome proliferator-activated receptor β (PPARβ) agonist or a retinoid X receptor (RXR) agonist to the subject diagnosed as having MSA.

The disclosure provides immune cells comprising a first activator receptor specific to CEA, and a second inhibitory receptor, and methods of making and using same for the treatment of cancer.

Incorporation of lipids into a growing hair fibre is provided by a composition comprising at least one of: 1) 0.05 to 8 wt % of a lipid precursor selected from the group consisting of a fatty acid having a chain of 6 to 24 carbon atoms, an ester or an acylglycerol thereof and mixtures thereof; 2) 0.05 to 8.0% of a "gene activator material" that modulates the biosynthesis of lipids in the hair follicle or sebaceous gland, selected from a) at least one activator of a peroxisome proliferator-activated receptor (PPAR activator), b) at least one activator of a liver X receptor (LXR), and c) at least one activator of a retinoid X receptor (RXR); and 3) a fatty alcohol having a chain of 6 to 24 carbon atoms, preferably 8 to 20 carbon atoms, most preferably 10 to 18 carbon atoms; and mixtures thereof; and a cosmetically acceptable carrier.

The invention relates to an anti-inflammatory and lipid-lowering-based nano preparation for treating fatty liver and a preparation method of the nano preparation. Galactose modified polyethylene glycol-polylactic acid-glycolic acid copolymer (PEG-PLGA) is used as a targeting carrier, and a lipid-lowering drug fenofibrate and an anti-inflammatory drug curcumin are co-loaded; the particle size of the nano preparation is 150-200nm, and the drug encapsulation efficiency is greater than or equal to 85%. Galactose modified PEG-PLGA is adopted as a carrier, galactose can be specifically combined with an asialoglycoprotein receptor (ASGPR) specifically expressed on the surface of liver cells, active targeting of the liver is achieved, the drug enrichment amount of the liver lesion position is remarkably increased, meanwhile, accumulation of drugs in extrahepatic tissue is reduced, extrahepatic toxicity is effectively reduced, and the drug delivery effect is improved. According to the present invention, the anti-inflammatory drug curcumin and the fenofibrate are combined, such that the biological safety of the preparation is improved, the lipid lowering drug fenofibrate and the anti-inflammatory drug curcumin are innovatively co-loaded, and the fenofibrate and the anti-inflammatory drug curcumin form the synergistic effect system: fenofibrate can activate peroxisome proliferator-activated receptor alpha (PPAR alpha), promote liver lipid catabolism, and reduce lipid deposition;

The present invention provides compounds as PPAR agonists and their application, involving a new class of peroxisome proliferator-activated receptor (PPAR) gamma receptor agonist, which can inhibit the production of mitochondrial reactive oxygen species, and most of which can readily cross the blood-brain barrier. The present invention also includes pharmaceutical uses of the compounds.

The invention discloses application of phenylpropionic acid as a PPAR-gamma agonist in preparation of a product for preventing, relieving and / or treating enteritis, relates to the technical field of medicines, and solves the problems that the existing medicines are poor in curative effect and do not have dual effects of preventing and relieving enteritis at the same time. Phenylpropionic acid is used as a PPAR-gamma agonist, can reduce infiltration of inflammatory cells into intestinal tissues by activating PPAR-gamma receptors and inhibiting expression of adhesion molecules, and can also regulate functions of immune cells, reduce release of inflammatory mediators, remarkably reduce generation of proinflammatory cytokines and effectively relieve intestinal inflammatory response, so that the intestinal inflammatory response is reduced, and the intestinal inflammatory response is reduced. Therefore, immune-mediated intestinal injury is relieved, immune response is adjusted, and the anti-inflammatory effect is remarkable; by inhibiting the expression of a fibrosis promoting factor, the process of intestinal fibrosis is slowed down or reversed, and complications such as intestinal stenosis are prevented.

The application discloses a biased polypeptide ligand of protease-activated receptor 2 and application thereof, and belongs to the technical field of proteins and polypeptides. The application aims to provide a biased polypeptide ligand of protease-activated receptor 2, which only activates the Gq signal pathway of PAR2. The application provides a biased polypeptide ligand of protease-activated receptor 2, which is obtained by any one or both of mutation and modification of amino acids of SLIGRL-NH2 as a starting sequence. The biased PAR2 polypeptide ligand designed in the application has unique advantages in treating diseases caused by nerve injury.

The present disclosure relates generally to processes for preparing seladelpar, an agonist of peroxisome proliferator-activated receptor (PPAR)-delta, and compositions thereof.

A compound having the structure of Formula I: wherein m=2 and n is an odd-number between 4 and 20, or a derivative thereof, or a salt, or a prodrug thereof, and a compound having the structure of Formula II: wherein m and n are independently an integer between 2 and 20, or a derivative thereof, or a salt, or a prodrug thereof are described. Compositions and methods of use of the compounds for therapeutically modulating peroxisome proliferator-activated receptors (PPARs) are also provided

The present invention relates to the use of skin benefit agents for enhancing the overnight repair function of skin, wherein the skin benefit agents are selected from the group consisting of: borage oil, farnesol, activators of the peroxisome proliferator-activated receptors, and mixtures thereof; and wherein the skin benefit agents are applied to the skin from about 5 pm to about 12 am at the end of the day.

The present invention is directed to an isotropic wash composition. The composition is stable, comprises alfa olefin sulfonate and a co-anionic surfactant. The composition comprises an amphoteric surfactant, low salt content and can comprise a peroxisome proliferator-activated receptor (PPAR) agonist.

The present disclosure provides novel V1a partial agonists for partially activating a V1a receptor. The partial V1a agonist has a therapeutic index of at least 20 (e.g., at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100). Also provided are method of treating liver fibrosis, cirrhosis, portal hypertension, ascites, esophageal varices, fundal varices, bleeding, arterial hypotension, and / or hepatorenal syndrome, including administering to a subject in need thereof a therapeutically effective dose of a composition including the V1a partial agonist(s) of the present disclosure, optionally in combination with a V2 antagonist.

Microparticulate (MP) formulations formed from one or more poly(hydroxyacid) polymers having a molecular weight ranging from 5kD to 60kD, and one or more active agents are injected into the eye of a subject to address eye disorders. The MP formulations assure high drug loading and extended delivery of the active agent of six to twelve months. The active agents may include peroxisome proliferator-activated receptor alpha (PPARα) signaling agonists such as PPARα agonist A190 (IUPAC name 3-((4-((4-fluorobenzyl)oxy)- 3- methylbenzyl)amino)benzoic acid). The formulations have therapeutic and protective effects against retinal degeneration diseases such as age-related macular degeneration (AMD), but may also be used for treating or relieving the symptoms of retinal inflammation, retinal neovascularization, retinal vascular leakage, retinopathy of prematurity (ROP), diabetic retinopathy (DR), and diabetic macular edema (DME).

The invention discloses a polypeptide, or a derivative and 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 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 be combined with GLP1R, 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 invention relates to oral analgesic compositions for alleviation of perceived nicotine irritation through inhibition or blocking of nicotine activated receptors or ion channels in the gastrointestinal tract, including the oral cavity. The composition of the invention comprises one or more nicotine sources, one or more buffering agents, and at least two antagonists in an effective amount to inhibit or block nicotine agonist activation of Nicotinic Acetylcholine Receptors (nAChR) and / or Transient Receptor Potential (TRP) ion channels, the at least two antagonists being selected from the group consisting of a first antagonist comprising camphor or one or more compounds resembling camphor, a second antagonist comprising eucalyptol, and a third antagonist comprising (1R,2S,5R)—N-(4-Methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamide (WS-12).

The invention discloses a polypeptide. The amino acid sequence of the polypeptide is an amino acid sequence of HAEAVFTDLSKYLDQAANFIIEWLWLSRRG or an amino acid sequence of a conservative modification form of the HAEAVFTDLSKYLDQAANFIIEWLWLSRRG. The polypeptide is a short sequence obtained through precise calculation and deep learning model optimization, can be combined with GLP1R, can effectively activate a GLP1R receptor, and can also be used for treating or preventing metabolic disorder related diseases such as obesity, diabetes, dyslipidemia related diseases, fatty liver diseases, metabolic syndromes and non-alcoholic fatty liver diseases.

The application provides a method for screening active ingredients capable of activating TAS1R3 receptors, and belongs to the technical field of screening of active ingredients of traditional Chinese medicines. The application establishes a biosensor, and the biosensor detects the current signal after each concentration of compound solution reacts with the TAS1R3 receptor; the dissociation constant K D of the interaction between the compound and the TAS1R3 receptor is calculated according to the linear fitting equation between the common logarithm of the concentration of the compound and the current change, and the compound with the K D value in the range of 10 ‑13 -10 ‑8 M is screened as the active ingredient capable of activating the TAS1R3 receptor. In the application, the interaction dissociation constant K D of the Atractylodes lactone II and the glycyrrhizic acid with the TAS1R3 protein is 3.759*10 ‑8 M and 4.435*10 ‑9 M respectively, and the binding force with the TAS1R3 protein is very strong. Moreover, the Atractylodes lactone II and the glycyrrhizic acid have the function of improving anemia within a certain concentration, and provide a new idea for the screening of candidate compounds with the sweet characteristic and the treatment of anemia or blood deficiency syndrome in traditional Chinese medicines and the research and development of new drugs.

The present invention relates to novel GLP-1 derivatives that are activating the GLP- 1 receptor in a way that favours a cAMP response and has an impaired beta-arrestin recruitment. More particular the present invention relates to such GLP-1 derivatives and their use for treatment of diseases such as diabetes and obesity.

The present invention relates to a new variant of EPO. In this study, the inventors identified a particular EPO differing from kidney-type EPO due to a different glycosylation pattern in patients with different diseases (for example idiopathic erythrocytosis, liver / kidney disorder, tumors...). This new EPO is similar to pre-term newborn EPO produced by the liver that differs from the normal EPO produced from renal interstitial cells due to different post-translational modifications (glycosylations). This new EPO shows an increased biological activity via activation of the EPO receptor (EPOR), that can explain the origin of erythrocytosis. The detection of this specific liver-like EPO could be used as a diagnostic tool to better adapt and follow the treatments of erythrocytosis patients or in other diseases associated with the overproduction of red blood cells. Thus, the invention relates to a specific EPO protein which differs from the EPO with kidney-type glycosylation pattern.

This invention provides for a fusion protein between a single chain TNFR2 Selective Agonist protein (seTNFR2 Selective Agonist) and a dimerization domain, such as an IgGFc protein. The single chain TNFR2 Selective Agonist moiety provides a theapeutic activity by selectively activating the TNFR2 form of the TNF-α receptor, thus selectively stimulating Tregs and / or increasing myelin deposition.

The present invention relates to one or more target-binding molecules, each comprising a binding domain [S1] and a binding domain [S2] that are each capable of binding to a scaffold protein, a binding domain [R1] that is capable of binding to a first receptor protein, and a binding domain [R2] that is capable of binding to a second receptor protein. The target-binding molecule is capable of inducing receptor signaling of a receptor complex, conditioned upon binding to a scaffold protein.