78 results about "Potency" patented technology

The invention discloses a multi-target joint optimized antibiotic molecule design system and method applied to the field of biological medicine, and the method comprises the steps: obtaining FabI enzyme and AcrAB-TolC efflux pump structure data, extracting double-target space and physicochemical characteristics, and constructing a joint pharmacophore model containing a FabI inhibition domain and an efflux pump blocking domain; screening candidate molecules meeting a double-domain space matching threshold, screening high-affinity double-target molecules through conformation sampling and free energy calculation, and forming a lead compound library through multi-layer filtration of metabolic stability, membrane penetrability, quantum chemical properties and synthesis feasibility; carrying out electron effect, chain length or heteroatom fine tuning on dominant molecules through in-vitro bacteriostasis and efflux inhibition experiment feedback, and carrying out iterative optimization until MIClt is met; 2 [mu] g / mL and the efflux inhibition rate is gt; according to the present invention, the antibacterial effect and the drug resistance inhibition ability are significantly improved, the molecular synthesizability and the biological safety are ensured, and the engineering design new path is provided for the Gram-negative bacterium drug resistance crisis.

Embodiments provide for methods of predicting glycation percentage of an amino acid in a therapeutic biomolecule. In one example, a method of predicting a glycation percentage of an amino acid in a biomolecule includes determining a first set of rates for a de-glycation reaction for a first set of temperatures, inferring a second set of one or more rate(s) for the de-glycation reaction for a second set of temperatures, and using the second set of one or more rate(s) to predict the glycation percentage at any temperature corresponding to the second set of temperatures and over any time duration. Also provided are methods for maintaining a glycation percentage of an amino acid within a predetermined glycation percentage range over a shelf-life of a therapeutic biomolecule, and methods for either reducing or increasing a potency of a therapeutic biomolecule in a subject at a time of administration.

The invention discloses a living body screening method of a high-throughput addiction inhibitor, which comprises the following steps: acquiring addictive nematodes with a plurality of addiction behavioral phenotypes; applying different addiction inhibitors to the addictive nematodes; the screening of the addiction inhibitors is realized according to the inhibition efficacy of the addiction inhibitors on the addiction behavioral phenotypes of the addiction nematodes, and based on the steps, the drug screening of the addiction inhibitors can be realized through the inhibition efficacy of the addiction inhibitors on the addiction behavioral phenotypes of the addiction nematodes in a high-throughput manner. Compared with the prior art, the medicine screening method of a traditional cell function system is abandoned, and medicine screening is carried out on the living animal behavioristics level in a brand new mode. Meanwhile, the advantages of easiness in large-scale culture, abundant behavioral modes and the like of the nematodes are utilized, and compared with expensive mammal feeding and experimental operation for drug screening, the method has higher cost performance, practical operability and high throughput.

The present application relates to azapeptide compounds of formula (I) derived from melanocyte-stimulating hormone release-inhibiting factor-1. A method to obtain compounds of formula (I) is also described herein. The compounds of formula (I) have been shown to be suitable for the treatment of dopamine-related disorders of the central nervous system. These compounds showed enhanced potency as positive allosteric modulators of the dopamine D2 receptors in comparison with the melanocyte-stimulating hormone release- inhibiting factor-1 and, in general, do not exhibit meaningful cytotoxicity.

The invention provides novel compounds which are peptide hormone analogues, and which are useful in treating disorders such as diabetes and obesity. The compounds of the general sequence recited in the specification possess a tailored profile with regards5 to potency properties at the GIP receptor. With regard to in vivo properties, administration of example peptides of the invention have been shown, in animal models, to result in increased weight loss. Preferred compounds achieve this without reducing food intake significantly.

Described herein are compositions, kits, and methods for potent delivery to a cell of a subject. The cell can be of a particular cell type, such as a basal cell. In some cases, the cell can be a lung cell of a particular cell type. Also described herein are pharmaceutical compositions comprising a therapeutic or prophylactic agent assembled to a lipid composition. The lipid composition can comprise an ionizable cationic lipid, and a selective organ targeting lipid. The lipid composition can further comprise a phospholipid. Further described herein are high-potency intravenous dosage forms of a therapeutic or prophylactic agent formulated with a lipid composition.

The invention discloses a halogen modified hapten for enhancing antibody titer and affinity as well as a preparation method and application of the halogen modified hapten, and belongs to the technical field of biochemical engineering. According to the method, an amantadine structure is innovatively and chemically modified, various halogens such as fluorine, chlorine and bromine are introduced, the AMA halogen modified hapten shown in the formula (I) is formed, and the traditional'most similar 'design principle is broken through. Compared with an unmodified hapten, the hapten modified by halogen in the invention has the advantages that the titer of the polyclonal antibody on amantadine can be obviously improved by 3.4-14 times; wherein the haptens A5 and A6 can obviously improve the titer of the monoclonal antibody to amantadine by 3-18 times, and the affinity is improved by 10.8-16.1 times. The invention provides a new thought and a new method for the rational design of the hapten of the small molecule compound and the preparation of the high-affinity antibody, and the related halogen modification type and quantity strategy can also provide valuable reference for the design of the hapten of other small molecule compounds.

The application provides a method for detecting the titer of vitamin B12 in a fermentation liquor. The method comprises the following steps: preparing a potassium dichromate solution, a hydrochloric acid solution and a potassium dihydrogen phosphate solution, mixing the three solutions with the vitamin B12 fermentation liquor under certain conditions to generate cyanocobalamin, and then testing the titer of the cyanocobalamin by using a high performance liquid chromatography. The titer of the vitamin B12 detected by using the method is consistent with the titer detected by using a sodium cyanide method. The operation method greatly reduces the safety risk of an analyst caused by using the sodium cyanide, and the operation method is simple, easy to manage in a laboratory and can save the testing cost.

The present disclosure discloses an alkanolamine multi-tailed lipid, a preparation method therefor, and a use thereof. The structural formulas of the lipid such as compound of Formula I, compound of Formula II or their stereoisomers, their tautomers, or their pharmaceutically acceptable salts:The ionizable lipid compound of the present disclosure maintains nanoparticle stability and delivery efficiency while simplifying LNP composition, offering advantages of high efficacy and low toxicity. Even under neutral conditions, the ionizable lipid compound can still adsorb mRNA through hydrogen bonding and van der Waals interactions. The synthesis method for the diethanolamine multi-tailed ionizable lipid of the present disclosure is straightforward. The ionizable lipid can be prepared on a large scale via a few addition reaction steps, which is convenient for high-throughput material screening.

The invention discloses a parameterized constraint system and method for efflux pump avoidance and off-target risk inhibition, which are applied to the field of biological medicines, and aims to solve the dual problem that toxic risks are caused by efflux pump mediated drug resistance enhancement and off-target combination of existing antibacterial drugs. The method comprises the following steps: constructing an efflux pump identification avoidance five-dimensional feature space and a target spot specificity geometric-electrical constraint boundary, performing structure mapping and deviation degree evaluation on candidate molecules, and triggering directional modification; the target matching is verified through molecular docking, and if the target does not reach the standard, the pharmacophore is locally adjusted; virtual screening is carried out based on an off-target protein database, a secondary structure disturbance mechanism is started for high-risk molecules, and a stereoisomerism or electrical reversal group is introduced to destroy non-target binding; according to the method, collaborative optimization of antibacterial efficacy, drug resistance avoidance and safety risk is achieved, and the research and development efficiency and druggability of candidate molecules are remarkably improved.

Methods for determining the function and / or activity and / or potency of isohydrolase proteins are provided.

The invention discloses an AKR1C3 selectively activated small molecule drug conjugate and application of the AKR1C3 selectively activated small molecule drug conjugate. The invention discloses a series of compounds with a structure as shown in a general formula I, and also discloses application of the compounds in cancer treatment. The inventor evaluates the efficacy of the compound represented by the general formula I in treatment of various cancers by taking an in-vitro anti-tumor cell experiment as a carrier, and finds that the compound has good in-vitro activity and extremely high selectivity and can be used as a precursor substance for further development of a cancer treatment effect through selective activation of aldoketoreductase 1C3.

To provide hepcidin analogs with improved in vivo half-lives, and related pharmaceutical compositions and methods of use thereof.SOLUTION: The present invention relates generally to hepcidin analog peptides and methods of making and using the same. In certain embodiments, hepcidin analogs exhibit one or more hepcidin activities. In certain embodiments, the present invention is directed to hepcidin peptide analogs comprising one or more peptide subunits, wherein the peptide subunits form a cyclized structure via an intramolecular bond, e.g., an intramolecular disulfide bond. In certain embodiments, cyclized structures have increased potency and selectivity compared to non-cyclized hepcidin peptides and analogs thereof. In certain embodiments, the hepcidin analog peptides of the present invention exhibit an extended half-life compared to hepcidin or conventional hepcidin analogs when delivered orally.SELECTED DRAWING: None

The present invention relates to cell-based methods for determining the biological activity of defibrotide. In particular, the invention provides a method for assessing the potency of defibrotide by assessing the viability of mammalian cells in the presence of at least one cytotoxic agent and one or more concentrations of defibrotide. Such methods are particularly useful for standardizing pharmaceutical compositions comprising defibrotide.

The present invention provides isolated Clostridium difficile binary toxin antibodies that are capable of neutralizing binary toxin with high potency, polypeptides and nucleic acids encoding the same, and methods of use thereof.

The present invention provides novel compounds that are peptide hormone analogs and are useful for treating disorders such as diabetes and obesity.The compounds of the general sequence listed herein have tailored profiles of potency at the GIP receptor.Regarding in vivo properties, administration of exemplary peptides of the present invention has been shown to result in improved weight loss in animal models.Preferred compounds achieve this without significantly reducing food intake.

Providing a method for testing the efficacy of andexanet. [Solution] This disclosure relates to a kit and method for measuring the potency of an andexanet sample in neutralizing a factor Xa inhibitor and restoring the activity of wild-type factor Xa. This disclosure provides a method for determining the activity of an andexanet sample, comprising: mixing a test sample containing an andexanet with a mixture containing human factor Xa (HFXa) and a direct factor Xa (fXa) inhibitor, wherein the molar ratio of FXa to Xa inhibitor is 0.2:1 to 0.3:1; adding a chromogenic fXa substrate to the mixture, wherein the chromogenic fXa substrate can release a chromophore upon reaction with HFXa; detecting the amount of chromophore released; and calculating the activity of the andexanet sample in releasing HFXa from a direct fXa inhibitor from the amount of chromophore released.

The invention provides modified apelin polypeptides having increased stability, circulating half-life, and / or potency relative to the native apelin-13 polypeptide. Compositions comprising the modified apelin polypeptides and methods of using the polypeptides for treating cardiac disorders, such as heart failure, are also disclosed.

The present application aims to provide a novel peptide which shows a rapid effect of drug efficacy and potency and has a long relief maintenance period, a medicament and an external agent containing the same, and particularly a preventive or therapeutic agent for dermatitis, rough skin, rhinitis, alopecia, thin hair, a hair growth agent, a hair growth promoting agent, an antipruritic agent, a skin care product, and the like. The present application achieves the above aim by providing an amino acid sequence represented by Formula I, a cyclic peptide or a derivative thereof having no peptide bond other than between the amino acids constituting the amino acid sequence, or a pharmaceutically acceptable salt thereof.

A new GLP-1 derivative, which has comparable or better potency, efficacy or efficacy, longer or comparable in vivo duration of action or in vivo half-life, has better or comparable GLP-1 receptor binding affinity, has better or comparable DPP-IV stability, compared to the marketed GLP-1 derivatives such as liraglutide, semaglutide, etc.

Disclosed is an application of Teruravone in the preparation of a drug for treating the amyotrophic lateral sclerosis disease. Teruravone can significantly increase the survival rate of TDP-43 M337V stably transfected cells and reduce the LDH leakage rate, and has a potency superior to that of Edaravone, indicating that Teruravone possesses stronger neuroprotective activity. Preliminary clinical trials indicate that after oral administration of Teruravone to an ALS patient for 3 months, the Norris Scale score and the neurofilament light chain protein level in the blood remained generally stable, and the decline in ALSFRS-R score was significantly slowed. Thus, the clinical effect of delaying the disease course of ALS is achieved, and no serious adverse effects were observed.

The present invention provides novel compounds which are peptide hormone analogs and are useful in the treatment of conditions such as diabetes and obesity. Compounds of the general sequence listed in the specification have a tailored profile with respect to potency characteristics for GIP receptors. Administration of example peptides of the invention has been demonstrated in animal models about in vivo characteristics to result in increased weight loss. Preferred compounds achieve this without significantly reducing food intake.

CD70 binding proteins or ligands, particularly CD27 polypeptides, and particularly variant CD27 extracellular binding domain polypeptides, are provided wherein the CD27 amino acid sequence is altered. The CD27 polypeptides and / or domains thereof, particularly the extracellular binding domains thereof are useful in the diagnosis and treatment of various conditions, including in cancer and immunotherapuetics. The CD27 polypeptides and / or domains thereof, particularly the extracellular binding domains thereof may also be used in lymphoid cell-mediated, including T cell-mediated, therapy, in chimeric antigen receptor (CAR) therapy, and / or in therapy in combination with chemotherapeutics, radiation therapy, immune modulators, cancer vaccines, cancer antigens, or anti-cancer agents. Particular variant CD27 polypeptides, extracellular domains, and novel CAR constructs are provided.

Processes to characterize classes and / or phenotypes are provided. In some instances, omic data is used to infer a class status or phenotype. Biomarkers for many potency phenotypes are also described.

In one aspect, the disclosure relates to compounds that inhibit Plasmodium falciparum asexual blood stage parasites (PfABS) In one aspect, the compounds exhibit sub-millimolar potency against the intraerythrocytic stages of Plasmodium falciparum and other Plasmodium species. In another aspect, the compounds are soluble in aqueous solutions at pH 7.4, making them suitable for oral administration to patients. Also disclosed are methods of making the compounds, pharmaceutical compositions comprising the same, and methods of treating or preventing malaria using the same. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

This invention relates to a novel polymorph of (1R,2R,3aS,3bR,10aS,10bR,11S,12aS)-5,10b-difluoro-1-(((fluoromethyl)thio)carbonyl)-11-hydroxy-2,10a,12a-trimethyl-7-phenyl-1,2,3,3a,3b,7,10,10a,10b,11,12,12a-dodecylhydrocyclopenta[5,6]naphtho[1,2-F]indazole-1-ylfuran-2-carboxylic acid ester as shown in formula (I), its preparation method, and its uses. The polymorph of this invention exhibits significant efficacy, good stability, high yield, and high purity, which is helpful for the selection and design of drug delivery routes and the determination of pharmaceutical formulation process parameters, thereby improving the quality of drug production. (I)

The present disclosure provides diazaspiro compounds represented by Formula (I), processes for their preparation, and pharmaceutical uses thereof, all within the field of medicinal chemistry. The diazaspiro compounds disclosed herein function as small-molecule agonists of the cholecystokinin-B receptor (CCK-BR). They exhibit excellent agonistic potency and demonstrate marked selectivity for CCK-BR over the cholecystokinin-A receptor (CCK-AR), thereby mitigating off-target effects and associated adverse reactions. No cardiotoxicity or other safety liabilities have been observed to date. The diazaspiro compounds are contemplated for the prophylaxis or treatment of disorders including, without limitation, epilepsy, depression, dementia, anxiety, Alzheimer's disease, tinnitus, amblyopia, schizophrenia, neuropathic pain, amnesia, gastric hyperacidity, obesity, pancreatic carcinoma, and gallbladder carcinoma.

The invention belongs to the field of biological medicine, and relates to application of a medicine for inhibiting or blocking conversion from PL to PLP in preparation of a medicine for treating ovarian cancer. According to the invention, through deep research on a mechanism that PL plays a role through targeting PPARalpha, it is identified that conversion of PL to PLP is an activity limitation bottleneck. On the basis, the combination of the PDXK inhibitor or the TNSALP activator and the PL is clear, and the killing efficacy of the PL on the ovarian cancer cells can be effectively improved. Furthermore, the PL is subjected to structural design, active groups of the PL are reserved, meanwhile, biotin groups are connected to metabolic sites of the PL, and the optimal compound Biotin-PL is screened out according to the binding capacity of the PL and a target PPAR alpha and the molecular structure stability. Experiments prove that Biotin-PL directly binds and activates a PPARalpha receptor and effectively blocks metabolic inactivation of PL to jointly play an ovarian cancer resisting role, the ovarian cancer resisting activity can be remarkably enhanced, and candidate molecules with good prospects are provided for developing novel ovarian cancer treatment drugs.