44 results about "Partial agonist" patented technology

The invention provides an application of liquiritin in preparation of a PPAR gamma receptor partial agonist. Through a structure-based high-throughput virtual screening technology, it is found that liquiritin can be used as a partial agonist of a PPAR gamma receptor, and the relative activation efficiency of liquiritin is 35.9% of that of rosiglitazone; in-vitro experiments prove that liquiritin can remarkably promote glucose uptake and consumption of HepG2 cells and does not induce adipocyte differentiation; in-vivo experiments prove that liquiritin can effectively improve the blood glucose level of an insulin resistance mouse model induced by high fat diet and reduce the level of serum proinflammatory factors. Compared with thiazolidinedione compounds, liquiritin not only can relieve and treat insulin resistance or related metabolic diseases, but also does not cause adverse reactions such as weight gain, fat accumulation and myocardial hypertrophy, provides a new candidate compound for developing safe and effective anti-diabetic drugs, and has a wide application prospect.

Provided herein are stable aqueous pharmaceutical compositions and formulation comprising non-naturally occurring melanocortin analogs. The non-naturally occurring melanocortin analogs may be partial agonists of the melanocortin 4 receptor with sub-micromolar or low-nanomolar binding activity. Certain non-naturally occurring melanocortin analogs may also be partial agonists or partial antagonists of the melanocortin 3 receptor.

The present technology comprises non-naturally occurring melanocortin analogs or pharmaceutically acceptable salts, solvates, or stereoisomers thereof and compositions comprising the same. The non-naturally occurring melanocortin analogs may be partial agonists the melanocortin 4 receptor with sub-micromolar or low-nanomolar binding activity. Certain non-naturally occurring melanocortin analogs may also be partial agonists or partial antagonists of the melanocortin 3 receptor.

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 technology comprises non-naturally occurring melanocortin analogs or pharmaceutically acceptable salts, solvates, or stereoisomers thereof and compositions comprising the same. The non-naturally occurring melanocortin analogs may be full agonists of the melanocortin 3 receptor and full or partial agonists of the melanocortin 4 receptor with sub-micromolar or low-nanomolar binding activity.

The present technology comprises stable aqueous pharmaceutical compositions and formulation comprising non-naturally occurring melanocortin agonist analogs. In some embodiments, the non-naturally occurring melanocortin analogs may be full agonists of the melanocortin 3 receptor (MC3R) and full or partial agonists of the melanocortin 4 receptor (MC4R) with sub-micromolar and / or low-nanomolar binding activity.

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.

The present technology comprises non-naturally occurring melanocortin analogs or pharmaceutically acceptable salts, solvates, or stereoisomers thereof and compositions comprising the same. The non-naturally occurring melanocortin analogs may be full agonists of the melanocortin 3 receptor and full or partial agonists of the melanocortin 4 receptor with sub-micromolar and / or low-nanomolar binding activity.

The present invention belongs to the field of pharmaceuticals. Disclosed in the present invention are a class of salt compounds of isosorbide mononitrate derivatives and the use thereof. Salts formed by the isosorbide mononitrate derivatives of the present invention and D-cycloserine exhibit dual activities as a nitric oxide donor and a partial NMDA receptor agonist. The present invention further relates to the use of the salts formed by the isosorbide mononitrate derivatives and D-cycloserine in a drug for treating cerebral stroke or the recovery period of cerebral stroke.

The present technology comprises non-naturally occurring melanocortin analogs or pharmaceutically acceptable salts, solvates, or stereoisomers thereof and compositions comprising the same. The non-naturally occurring melanocortin analogs may be full or partial antagonists of the melanocortin 3 receptor with sub-micromolar or low-nanomolar binding activity. Some of the non-naturally occurring melanocortin analogs may also be full or partial antagonists or partial agonists of the melanocortin 4 receptor with sub-micromolar or low-nanomolar binding activity.

Methods and compositions for preventing an immune response to an immunogenic therapeutic agent [i.e. anti-drug antibody (ADA), a.k.a. anti-therapeutic antibody (ATA)] are disclosed. One of the disclosed methods comprises administering an effective amount of an immunosuppressant such as an Interleukin-2 (IL-2) signaling pathway inhibitor, including an antagonist, super agonist or partial agonist to the cytokine IL-2, to the IL-2 receptor (IL-2R), or to IL-2R signal transduction molecules. Inhibitors can be in the form of antibodies or antibody fragments, peptide inhibitors, fusion molecule, small molecules, antibody / small molecule conjugates. Administration of a given inhibitor can decrease the incidence and / or magnitude of an immune response or prevent an immune response, including an antibody response, to a potentially immunogenic therapeutic agent in a non-human primate (NHP). Some of the disclosed methods produce a tolerizing effect in NHPs.

Compounds having opioid characteristics are provided that can be used for various therapeutic methods including the treatment of pain and opioid use disorders, and compounds having opioid antagonist properties that can be used to treat opioid overdoses. These compounds include agonists and antagonists having selective activity toward more one or more opioid receptors. Such compounds can be full or partial agonists, or can be antagonists lacking agonist properties toward delta and kappa opioid receptors. The partial agonists can diminish side effects associated with traditional opioid medications, and the antagonists can overcome respiratory depression caused by potent narcotics. Structurally these compounds include constrained piperidines with alkenyl or cyanoalkyl groups, as well as other substituents providing desired properties.

An intestine-specific partial agonists of farnesoid X receptor (FXR) is disclosed, along with methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with FXR activity.

The present disclosure includes peripheral partial agonists of one or more CB receptors, including modulation of CB1, both with and without CB2 selectivity. The compounds of the present disclosure may be useful in the treatment of diseases and disorders mediated by a CB-signaling pathway, including but not limited to pain, gastrointestinal disorders, metabolic disorders, and liver disorders, such as alcoholic steatohepatitis or nonalcoholic steatohepatitis (NASH).

The invention relates to oleoyl-lysophosphatidy linositol (oleoyl-LPI) and new synthetic derivatives thereof and uses thereof, and to pharmaceutical compositions comprising such compounds. The invention provides activators and / or up-regulators of glucoregulatory hormones such as glucagon like peptide-1 (GLP-1), and more specifically to agonists, partial agonists and reverse antagonists of GPR119 or activators of GLP-1 activity and / or synthesis and / or secretion, and pharmaceutical compositions comprising same, uses thereof in therapy of diabetes, obesity and other metabolic disorders.

The invention discloses a biphenyl compound as well as a preparation method, an intermediate, a pharmaceutical composition and application thereof. Specifically provided is a compound represented by formula I or a pharmaceutically acceptable salt thereof. The compound has good retinoic acid receptor gamma agonist activity and selectivity, almost has no agonist activity on retinoic acid receptors alpha and / or beta, and is beneficial to reduction of systemic side effects; more preferably, the compound has moderate partial agonistic activity, is small in skin irritation, less in adverse reaction and excellent in safety and compliance under the condition of maintaining the drug effect, effectively solves the ubiquitous problems of the existing RAR compounds, and can be used for treating and preventing diseases related to the retinoic acid receptor gamma. # imgabs0 #

The present technology comprises non-naturally occurring melanocortin analogs or pharmaceutically acceptable salts, solvates, or stereoisomers thereof and compositions comprising the same. The non-naturally occurring melanocortin analogs may be partial agonists of the melanocortin 4 receptor with sub-micromolar or low-nanomolar binding activity. Certain non-naturally occurring melanocortin analogs may also be partial agonists or partial antagonists of the melanocortin 3 receptor.

The present invention relates to compounds of Formula X, stereoisomers, tautomers, or mixtures thereof, pharmaceutically acceptable salts, co-crystals, polymorphs, or solvates of the compounds, or stable isotopic derivatives, metabolites, or prodrugs of the compounds. As NLRP3 modulators (e.g., agonists or partial agonists), these compounds are useful in the treatment of diseases of abnormal cell proliferation (e.g., cancer).

The present technology comprises non-naturally occurring melanocortin analogs or pharmaceutically acceptable salts, solvates, or stereoisomers thereof and compositions comprising the same. The non-naturally occurring melanocortin analogs may be full or partial antagonists of the melanocortin 3 receptor with sub-micromolar or low-nanomolar binding activity. Some of the non-naturally occurring melanocortin analogs may also be full or partial antagonists or partial agonists of the melanocortin 4 receptor with sub-micromolar or low-nanomolar binding activity.

The present technology comprises non-naturally occurring melanocortin analogs or pharmaceutically acceptable salts, solvates, or stereoisomers thereof and compositions comprising the same. The non-naturally occurring melanocortin analogs may be full agonists of the melanocortin 3 receptor and full or partial agonists of the melanocortin 4 receptor with sub-micromolar or low-nanomolar binding activity.

The present technology comprises non-naturally occurring melanocortin analogs or pharmaceutically acceptable salts, solvates, or stereoisomers thereof and compositions comprising the same. The non-naturally occurring melanocortin analogs may be partial agonists the melanocortin 4 receptor with sub-micromolar or low-nanomolar binding activity. Certain non-naturally occurring melanocortin analogs may also be partial agonists or partial antagonists of the melanocortin 3 receptor.

Provided are Toll-like receptor 7 / 8 agonist compounds that facilitate local release and / or local retention of the bioactive form of a TLR7 / 8 agonist and reduce an unwanted systemic inflammatory cytokine response. 【Solution means】 Formula (I): F-[W-L 3 -L 2 -L 1 -D]x(I) [wherein, D is a TLR7 / 8 agonist moiety, L 1 is a linking or self-detachable linker, L 2 is a cleavable linker, L 3 is a conjugation linker, W is O, S or NR 10 wherein, R 10 is H or C1-C8 alkyl, x is an integer from 1 to 500, F is a conjugation moiety, and the TLR7 / 8 agonist moiety is a 1H-imidazo[4,5-c]quinoline derivative]. Compounds are provided.

Disclosed are methods of alleviating or preventing one or more symptoms associated with fragile X syndrome in an individual in need thereof via administration of a therapeutically effective amount of a GABA(A) alpha 2 and / or 3 partial agonist. The one or more symptoms may include impaired functional communication, anxiety, inattention, hyperactivity, sensory reactivity, autonomic nervous system dysregulation, aberrant eye gaze, self-injury, aggression, seizures, EEG abnormalities, including but not limited to, abnormal spectral analysis, event related potentials which may include auditory and visual responses, abnormalities in cortical responses as evoked by transcranial magnetic stimulation including resting and active motor thresholds and abnormal responses in measures of cortical inhibition and excitation, aberrant impaired cognitive function, compromised daily living skills, or a combination thereof.

Disclosed are compounds having selectivity towards a serotonin 2 receptor (5-HT2), including 5-HT2A, 5-HT2B, and / or 5-HT2C, including a compound which is formula (I); (N-(2-(lH-indol-2-yl)ethyl)-2-(lH-indol-3-yl)-N-methylethan-1 -amine), or a pharmaceutically acceptable salts of the compounds. Methods and uses of the compounds in treating conditions treatable by agonism of 5-HT2A and / or 5-HT2C, the methods and uses comprising administering a disclosed compound to a subject in need thereof, are also disclosed.

A method of screening for a candidate substance according to the ability of the candidate substance to modulate RAGE activity wherein such RAGE activity is induced by a co-localized active-type GPCR, the method comprising the steps of contacting a RAGE polypeptide with a GPCR polypeptide in the presence of a candidate substance, wherein the GPCR polypeptide is constitutively active and / or activated by the addition of an agonist, a partial agonist or an allosteric modulator of the GPCR; and detecting whether the candidate substance is a modulator of RAGE ligand-independent RAGE activation by co-localized activation-type GPCR by detecting an effect indicative of RAGE activation modulated by the presence of the candidate substance and / or by detecting RAGE-dependent signaling modulated by the presence of the candidate substance.

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.

This invention pertains to the field of inflammatory bowel disease and relates to a quaternary ammonium salt-based locally acting sphingosine 1-phosphate receptor subtype 1 agonist. The compounds, their stereoisomers, and pharmaceutically acceptable salts of this application are locally acting S1PR1 agonists. These compounds exhibit good agonistic activity against sphingosine 1-phosphate receptor subtype 1, are almost not absorbed orally, and have low oral bioavailability. However, they still possess good in vivo anti-ulcerative colitis activity, improving intestinal inflammatory damage in mice with ulcerative colitis, increasing mouse weight, and increasing colon length. Therefore, these compounds, while maintaining in vivo anti-ulcerative colitis activity, can reduce the risk of infection caused by systemic immunosuppression. The structural formula of the sphingosine 1-phosphate receptor subtype 1 agonist is shown in Formula I.

Provided herein are pharmaceutical compositions of non-naturally occurring melanocortin analogs formulated for oral administration. The non-naturally occurring melanocortin analogs may be partial agonists of the melanocortin 4 receptor with sub-micromolar or low-nanomolar binding activity. Certain non-naturally occurring melanocortin analogs may also be partial agonists or partial antagonists of the melanocortin 3 receptor.

The present technology comprises non-naturally occurring melanocortin analogs or pharmaceutically acceptable salts, solvates, or stereoisomers thereof and compositions comprising the same. The non-naturally occurring melanocortin analogs may be partial agonists the melanocortin 4 receptor with sub-micromolar or low-nanomolar binding activity. Certain non-naturally occurring melanocortin analogs may also be partial agonists or partial antagonists of the melanocortin 3 receptor.