63 results about "Partial agonist" patented technology

Disclosed herein novel dopamine D3 receptor selective antagonists / partial agonists compounds with high affinity and metabolic stability useful for the treatment of psychiatric and neurological disorders and as research and diagnostic tools. Also disclosed are methods of making the compounds.

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, inter alia, are human interleukin-2 (IL-2) muteins or variants thereof. In particular, provided herein are IL-2 muteins that have a decreased binding capacity for IL-2Rγ. Such IL-2 muteins are useful, for example, as IL-2 partial agonist in applications where reduction or inhibition of one or more IL-2 and / or IL-15 functions is useful (e.g., in the treatment of autoimmune diseases or conditions). Also provided are nucleic acids encoding such IL-2 muteins, methods of making such IL-2 muteins, pharmaceutical compositions that include such IL-2 muteins and methods of treatment using such pharmaceutical compositions.

A method of treating and attenuating L-DOPA-induced dyskinesia, comprising administering an effective dose of at least one pharmacological agent, e.g., vilazodone, having serotonin-specific reuptake inhibition (SSRI) and serotonin receptor 1A (5-HT1AR) partial agonism activity, in conjunction with L-DOPA. Other agents, such as an L-DOPA decarboxylase inhibitor, e.g., carbidopa, or other adjunct treatments may also be provided.

Provided are embodiments of para-substituted 1,1-dialkyl-4-phenylpiperazin-1-ium iodides advantageous for modulating inflammation that have been synthesized and their electrophysiology activities for α9, α9α10, and α7 nAChRs compared. The para position contained alkyl or aryl amides, or heterocyclic isosteres for the amide, and the alkyl groups were varied at the ammonium piperazine nitrogen to see if compensatory changes in size at this position of the molecule impacted function. The compounds were characterized with two-electrode voltage-clamp measurements on Xenopus oocytes expressing nAChRs. General, the compounds were more potent for α9-containing receptors than for α7, and the majority were either full or strong partial agonists for α9-containing nAChR.

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

A process for the synthesis of (R)-N-(4-(4-(3-chloro-5-ethyl-2-methoxyphenyl) piperazin-1-yl)-3-hydroxybutyl)-1H-indol-2-carboxamide (Compound 8) is described, as well as the intermediate compounds of formulae 5-7, 9 and 14 for use in said process, as well as a process for the synthesis of (R)-N-(4-(4-(3-chloro-5-ethyl-2-methoxyphenyl) piperazin-1-yl)-3-hydroxybutyl)-1H-indol-2-carboxamide (Compound 8). # imgabs0 #

Novel human interleukin-2 (IL-2) muteins or variants thereof are provided. In particular, provided are IL-2 muteins that have an increased binding capacity for IL-2Rβ receptor and a decreased binding capacity for IL-2Rγc receptor, as compared to wild-type IL-2. Such IL-2 muteins are useful, for example, as IL-2 partial agonist and antagonists in applications where reduction or inhibition of one or more IL-2 and / or IL-15 functions is useful (e.g., in the treatment of graft versus host disease (GVHD) and adult T cell leukemia). Also provided are nucleic acids encoding such IL-2 muteins, methods of making such IL-2 muteins, pharmaceutical compositions that include such IL-2 muteins and methods of treatment using such pharmaceutical compositions.

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.

A method of screening candidate agents for their ability to modulate RAGE activity where such RAGE activity is induced by an active co-located GPCR, the method comprising the steps of: contacting a RAGE polypeptide with a GPCR polypeptide in the presence of a candidate agent where the GPCR polypeptide is constitutively active and / or is activated by addition of an agonist, partial agonist or allosteric modulator of that GPCR; and detecting whether the candidate agent is a modulator of RAGE ligand-independent activation of RAGE by activated co-located GPCR by detecting an effect indicative of modulation of RAGE activation by the presence of the candidate agent and / or by detecting RAGE-dependent signalling that is modulated by the presence of the candidate agent.

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 invention provides a piperazine derivative, as shown in formula (I) or its stereoisomers and pharmaceutically acceptable salts thereof; the piperazine derivative provided by the present invention has a strong affinity for dopamine D2, D3, and 5-HT1A, 5-HT2A receptors of 5-hydroxytryptamine, and has a medium affinity for dopamine D4 and 5-HT2C, 5-HT7 of 5-hydroxytryptamine and α1-adrenaline, histamine H1 receptors, and also has a medium affinity for 5-hydroxytryptamine reuptake sites, and has no obvious affinity for cholinergic muscarinic receptors. Functionally, it is a partial agonist of D2 and 5-HT1A receptors and an antagonist of 5-HT2A receptors, and can be used to treat or prevent diseases that require regulation of one or more of dopamine D2 receptors, 5-HT1 receptors, 5-HT2 receptors, 5-HT7 receptors, α1-adrenaline receptors, histamine H1 receptors and 5-hydroxytryptamine reuptake sites.

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.

Disclosed herein are compositions and methods for treating opioid use disorders, including opioid overdose with combinations including methocinnamox and at least one additional opioid modulators, for example opioid agonists, partial agonists, antagonists and allosteric modulators. The compositions and methods are also useful for treating alcohol use disorder, and other disorders associated with endogenous opioid production.

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.

Disclosed herein are novel methods of treating substance use disorders, mitigating the development of substance addiction, reducing the severity of substance withdrawal symptoms, or reducing or preventing substance relapse by providing to the patient a therapeutically effective amount of a Medication Assisted Treatment agent and a selective dopamine D3 receptor antagonist / partial agonist. In addition, the D3 antagonists / partial agonists described herein may be used to augment the effectiveness of current Medication Assisted Treatment regimens (e.g. methadone or buprenorphine) for the treatment of substance use disorders, including opioid use 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.