17 results about "Agonist substance" patented technology

The invention relates to the technical field of biomedicine, and discloses an application of miR-3963 for improving insulin resistance in preparation of drugs. The invention provides application of an active component in preparation of a medicine for preventing and / or treating insulin resistance or insulin resistance related diseases. The active component comprises miR-3963 or other substances (such as miR-3963 agonists, mimics and the like) capable of increasing the content of miR-3963 in a body. Research finds that miR-3963 can respond to insulin stimulation increase, and the activity of an insulin signal channel is enhanced by targeted inhibition of expression of an SMPD1 gene, so that insulin resistance is effectively improved. According to the invention, a novel target with great potential is provided for developing a new generation of targeted drugs aiming at the root of diabetes, and a key clue is provided for the miRNA participating in the blood glucose homeostasis regulation and the generation mechanism of insulin resistance.

The present invention relates to a compound of formula (I) wherein R1 represents H, (C1-C6)alkyl-; hydroxy-(C1-C6)alkyl-; NH2—(C1-C6)alkyl-; NH—(C1-C6)alkyl-(C1-C6)alkyl-; N((C1-C6)alkyl)2-(C1-C6)alkyl-; (C2-C6)alkenyl-; (C2-C6)alkynyl-; phenyl(C1-C6)alkyl-; (C3-C10)cycloalkyl(C1-C6)alkyl-; (C3-C10)membered heterocycloalkyl(C1-C6)alkyl-; (C5-C10)membered heteroaryl(C1-C6)alkyl-; (C3-C10)membered heterocycloalkyl-NH—(C1-C16)alkyl-; and (C3-C10)membered heterocycloalkyl-N(C(O)—(C1-C6)alkyl)-(C1-C16)alkyl-; R2 represents a halogen atom, a (C1-C6)alkyl- group or other well defined groups; and R3 represents a deuterium atom; H, (C1-C6)alkyl-; (C2-C6)alkenyl-; (C2-C6)alkynyl-; (C1-C6)alkylthio-; —OR6; —NR7R8; (C3-C10)membered heterocycloalkyl-; (C5-C10)membered heteroaryl-; —(C6-C10)membered aryl; and (C3-C10)cycloalkyl-. The present invention further relates to intermediates of these compounds, processes for their preparation, a medicament and a pharmaceutical composition comprising them, and their therapeutic uses, in particular as TLR7 and / or TLR8 agonists, as well as their use in a vaccine.

The invention discloses a cell membrane bionic magnetic nano-microsphere based on cannabinoid receptor CB2 receptor targeting, a preparation method of the cell membrane bionic magnetic nano-microsphere and application of the cell membrane bionic magnetic nano-microsphere to analgesic screening. The cell membrane bionic magnetic nano-microsphere takes a surface aldehyde group modified magnetic nano-microsphere as a core; a cell membrane of a high-expression cannabinoid receptor CB2 is wrapped on the surface of a magnetic bead by using a covalent bond binding method, a potential agonist is screened based on ligand-receptor affinity interaction, the active ligand of the cannabinoid receptor CB2 is efficiently captured by using a bionic magnetic nano material fishing technology, active components can be rapidly and sensitively screened out, and the application prospect is wide. The method is simple in operation, reduces analysis steps and time, improves analysis accuracy, remarkably improves separation efficiency and specificity of trace active components in a complex system by adopting collaborative innovation of a magnetic nano material and a biomimetic membrane technology, and has a great application prospect.

There is disclosed a compound of Formula (I):and any pharmaceutically acceptable salt or zwitterion thereof, wherein: R is hydrogen, methyl or ethyl; R1 is hydrogen or C1-C2 alkoxy; R2 is methyl or a C2-C4 group which may be saturated or unsaturated, branched or linear; and R3, R4, R5 and R6 each are independently selected from hydrogen, hydroxyl, halogen, methyl optionally substituted with hydroxy, methoxy, ethoxy, and a saturated or unsaturated C2-C3 that may be optionally substituted with hydroxyl, with the provisos that: (i) at least two of R4, R5, R6 and R7 must be hydrogen, and (ii) R3, R4, R5 and R6 may be selected such that an adjacent pair thereof join to form a ring having at least 5 members. The compound of Formula (I) is believed useful in treating a disease or disorder in a subject which may be alleviated by a 5HT2A agonist (e.g., CNS disorders and one or more symptoms of any one of depression, alcoholism, tobacco addiction, cocaine addiction, inflammation, cluster headache and PTSD in a subject).

The invention relates to a method for determining the ability of a molecule to modulate the activation of a G protein-coupled receptor (GPCR), said method comprising the following steps:a) introducing, in a first container:a membrane preparation bearing one or more GPCRs and one or more alpha G-proteins,a source of nonhydrolyzable or slowly hydrolyzable GTP labeled with a first member of a pair of RET partners,a ligand of the alpha subunit of a G protein (alpha G-protein) labeled with a second member of the pair of RET partners, said ligand being capable of binding to the full alpha G-protein bound to the nonhydrolyzable or slowly hydrolyzable GTP labeled with the first member of a pair of RET partners,optionally a GPCR agonist;b) measuring the RET signal emitted in the first container;c) introducing (i) in a second container, the same reagents as in step a) and the molecule to be assayed or (ii) in the first container, the molecule to be assayed;d) measuring the RET signal emitted in the second container or in the first container obtained in step c);e) comparing the signals obtained in steps b) and d), a modulation of the signal obtained in step d) relative to that obtained in step b) indicating that the molecule to be tested is capable of modulating the activation of the GPCR.

The invention discloses a medicine for relieving pain. The medicine contains a compound which is used for acupoint administration and is used for targeted excitation of Piezo1 protein. The invention further discloses application of the Piezo agonist in preparation of the medicine for relieving pain. The invention relates to application of a Piezo agonist in relieving neuropathic pain after peripheral nerve injury, and provides a novel non-central analgesic treatment choice for neuropathic pain through a targeted peripheral mechanism. Micro-injection only needs to be carried out at the acupuncture point, systemic side effects of a traditional analgesic medicine are effectively avoided, the central safety is high, the addiction risk is avoided, compared with 20-30 minutes of needle retaining time generally needed by traditional acupuncture treatment of a single acupuncture point, the time consumed by acupuncture point injection is remarkably shortened, and the clinical efficiency requirement is better met.

The invention discloses a screening method, system and device based on molecule generation and activity prediction and a medium. The screening method comprises the following steps: S1, collecting an active molecule sample; s2, preprocessing the collected active molecule samples to generate standardized molecule data; s3, predicting the activity of the standardized molecular data; and S4, screening the standardized molecular data. The method is suitable for molecular screening in the field of drug discovery, and compared with the prior art, the method has the following advantages that efficient generation is achieved, specifically, molecules related to specific targets are rapidly generated through transfer learning, and the experimental screening range is reduced; the ROC values of the activity prediction model on a BindingDB database and a DAVIS database respectively reach 0.968 and 0.989, so that the screening precision is remarkably improved. And comprehensive screening: combining a molecular docking technology to further verify a molecular binding mode and improve the experiment success rate. In conclusion, the method is particularly suitable for active molecule discovery of novel targets (such as STING agonists), the research and development period can be remarkably shortened, and the experiment cost can be reduced.

The invention discloses a medicinal composition of a triple compound inhalation preparation as well as a preparation method and application of the medicinal composition, and relates to the technical field of respiratory system medicinal preparations. According to the pharmaceutical composition, the pharmaceutical composition which is convenient to use and better in effect can be obtained by compounding the ingredients of the pharmaceutical composition, the problem of non-uniform mixing of the ingredients with high dose difference is solved through a step-by-step mixing process, the powder flowability is ensured, the lung delivery efficiency is improved, and the pharmaceutical composition is suitable for clinical application. The medicine can be suitable for maintenance treatment of asthma or chronic obstructive pulmonary disease, and can also prevent acute exacerbation of chronic obstructive pulmonary disease and / or improve the symptom severity of acute exacerbation of chronic obstructive pulmonary disease.

There is disclosed a compound of Formula (I):and any pharmaceutically acceptable salt or zwitterion thereof; wherein: R is hydrogen, methyl or ethyl; R1 is hydrogen or C1-C2 alkoxy; R2 is methyl or a C2-C4 group which may be saturated or unsaturated, branched or linear; and R3, R4, R5 and R6 each are independently selected from hydrogen, hydroxyl, halogen, methyl optionally substituted with hydroxy, methoxy, ethoxy, and a saturated or unsaturated C2-C3 that may be optionally substituted with hydroxyl, with the provisos that: (i) at least two of R4, R5, R6 and R7 must be hydrogen, and (ii) R3, R4, R5 and R6 may be selected such that an adjacent pair thereof join to form a ring having at least 5 members. The compound of Formula (I) is believed useful in treating a disease or disorder in a subject which may be alleviated by a 5HT2A agonist (e.g., CNS disorders and one or more symptoms of any one of depression, alcoholism, tobacco addiction, cocaine addiction, inflammation, cluster headache and PTSD in a subject).

The invention relates to a temperature-sensitive liposome with synergistic anti-tumor efficacy, the temperature-sensitive liposome is prepared from active substances and a carrier material, the active substances comprise a near-infrared photothermal agent IR780 and an STING agonist, and the carrier material comprises a lipid material, a surface modification lipid material and a phase change material. According to the invention, the space structure of a lipid bilayer and a water phase core is utilized, and efficient co-loading of a near-infrared photothermal agent IR780 and an STING agonist DMXAA is realized in the same temperature-sensitive liposome. According to the temperature-sensitive liposome disclosed by the invention, a cascade process of photo-thermal treatment, phase change, drug release and immune activation can be realized, and a synergistic anti-tumor effect superior to that of pure photo-thermal treatment or single STING agonist treatment is shown.

The application discloses a kind of mannose modified graphene oxide-based nano drug delivery systems and its preparation method and application, belong to the technical field of biomedical materials and pharmaceutical preparations.The application solves the current free drug in vivo exposure shortage, lack of myeloid cell directional regulation, drug release uncontrollable and drug system biological compatibility problem.The application synthesizes mannose grafted ethylenediamine EDM, then with GO, EDM, EDC and NHS reaction, promote GO surface carboxyl and EDM amino form amide bond, obtain carrier, with DTX and Vadimezan loaded on carrier to obtain drug delivery system.The application uses GO as matrix, realizes receptor-mediated targeting nano-carrier system by surface functionalization of mannose, and it is used to deliver hydrophobic chemotherapeutic drugs and immune stimulants, which can be used for tumor treatment, including inhibiting primary tumor growth and metastasis-related lesions, and the effect is more obvious in combination with near-infrared light thermal response.

The invention discloses a cembrane type diterpenoid compound as well as a preparation method and application thereof. The invention relates to a series of cembrane type diterpenoid compounds extracted and separated from Boswellia sacra Flue. Resin as well as a preparation method and application of the cembrane type diterpenoid compounds, and belongs to the technical field of medicines. The structure of the cembrane type macrocyclic diterpenoid compound is determined by adopting separation methods such as silica gel column chromatography, ODS column chromatography, Sephadex LH-20 column chromatography, high performance liquid chromatography (HPLC) and the like and combining multiple spectroscopy technologies such as nuclear magnetic resonance spectrum and the like. The compounds can activate TRPV3 ion channel proteins, and have great application prospects in preparation of TRPV3 agonists and in preparation of drugs and skin care products for promoting skin renewal and repair.

The invention discloses a high-throughput and high-sensitivity screening method for endogenous itching-causing substances and application of the high-throughput and high-sensitivity screening method. According to the invention, firstly, endogenous itching-causing substances are screened out through a metabonomics technology, and then are verified through combination of a NanoBiT-based MRGPR detection system and an in-vivo experiment, so that integrated screening of the endogenous itching-causing substances in systemic disease itching is realized, and the defects of single discovery and screening mode of pruritus in systemic disease itching at present, low screening efficiency and the like are overcome. And breakthrough progress is not made yet. A cholestatic pruritus mouse is taken as an object, and the endogenous substance LPC (18: 1) screened from the cholestatic pruritus disease has strong activation and selectivity of the Mrgpra1 pruritus receptor, and can be used as an Mrgpra1 pruritus receptor agonist tool molecule for screening a tool medicine taking the Mrgpra1 pruritus receptor as a target spot.

The present invention relates to a cosmetic skin lightening composition comprising the combination of sclareolide, kojic acid and ascorbyl glucoside, wherein kojic acid is encapsulated within a targeted microcapsule or nanocapsule having a melanocortin 1 receptor (MC1R) agonist peptide bound to the surface. It was found that such combination of active substances provided synergistic kin-whitening effect. The present invention also relates to the cosmetic use of this composition for skin whitening, particularly, for the elimination or reduction of hyperpigmented marks of the skin, such as UV exposure related marks, post-scar marks, post-inflammation marks, melasma marks, lentigo marks or age-related marks.