15 results about "Therapeutic index" patented technology

The application discloses a high-safety tumor treatment preparation based on a prodrug-enzyme-neutralizing antibody three-system, and a preparation method and application thereof. The preparation comprises three core components: (a) a prodrug, which is coupled by an anti-tumor drug (such as doxorubicin) and cephalosporin; (b) an activating enzyme, such as beta-lactamase, which is specifically expressed in the tumor by phage, catalyzes the hydrolysis of the prodrug, and releases the active drug; and (c) a neutralizing antibody, such as an anti-doxorubicin monoclonal antibody, which can specifically bind and neutralize the active drug overflowing into the blood circulation. The application first integrates the precise killing strategy of "prodrug-local activation" and the safety strategy of "neutralizing antibody-systematic protection" into a complete treatment closed loop, utilizes the "differential neutralization" characteristics of the anti-doxorubicin antibody, effectively protects normal tissues from toxic damage under the premise of not affecting the local efficacy of the tumor, and significantly improves the therapeutic index of the chemotherapy drug, reduces the side effects such as cardiotoxicity and bone marrow suppression, and provides a new paradigm with high efficiency and safety for tumor treatment.

The application discloses a cannabidiol derivative and application thereof, and belongs to the technical field of medicinal chemistry. The structural general formula of the cannabidiol derivative is shown as formula (I): (I) R1 is selected from one of hydrogen, chlorine, bromine, a hydroxyl group, a cyano group, an acetoxy group, an acryloyloxy group, a benzoyl group, an acetamide group, an acrylamide group, a propiolamide group, an ethyl thiourea group, a 3-chloro-2,2-dimethylpropionyl group, a 2-ethylsulfonamide acetyl group, a 2-ethylsulfonamide-N-(2-amino-2-oxoethyl) acetyl group, a methylsulfonyl group, an ethylsulfonyl group, a vinylsulfonyl group, an alkyne propylsulfonyl group, a phenylsulfonyl group and a styrylsulfonyl group; and R2 is selected from one of C2-C5 alkyl groups. The cannabidiol derivative disclosed by the application has significantly improved anti-neuroinflammatory activity, significantly reduced cytotoxicity, and a generally improved treatment index of more than 10 times, or even more than 260 times, compared with cannabidiol.

The application discloses application of BMS-833923 and derivatives thereof and a medicine, and belongs to the technical field of antibiotics. The BMS-833923 and the derivatives thereof can be used as colistin adjuvants to jointly inhibit or eliminate gram-negative bacteria, and can also independently inhibit or eliminate gram-positive bacteria. The gram-negative bacteria can include at least one of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, pan-drug-resistant strains BAA-1800, BAA-1794 and BAA-1792, and the gram-positive bacteria can include at least one of Staphylococcus aureus and Bacillus subtilis. By taking the BMS-833923 and the derivatives thereof as adjuvants of colistin, the therapeutic index of the colistin can be effectively expanded, and lower, non-toxic doses of the colistin can be used in clinical treatment of effective treatment of drug-resistant bacterial infections.

This invention provides a liver-targeting glycoligand molecule modified with dual-antenna GalNAc and its drug delivery system. This liver-targeting glycoligand molecule and its drug delivery system, through ASGPR recognition, can maximize the concentration of therapeutic drugs in liver tumor parenchymal cells, thereby improving the targeting of drug distribution, increasing the therapeutic index, reducing systemic toxicity, and improving patient survival time and quality of life. The liver-targeting glycoligand molecule of this invention is synthesized using an enzymatic synthesis method, which involves fewer synthesis steps, mild enzymatic reaction conditions, high regioselectivity, high reaction efficiency, is environmentally friendly, and has low production costs, making it highly promising for industrialization.

The present disclosure provides a modified bispecific molecule that targets (a) a tumor-specific mutant peptide or mutation-associated neoantigen (MANA) presented by human leukocyte antigens (HLA) on the surface of target cancer cells; and (b) a surface protein (e.g., CD3) expressed on effector immune cells (e.g., T cells), as well as a method of using the molecule in cell therapy to diagnose, prevent, and / or treat human diseases including cancer. The bispecific molecule is modified to additionally include domain orientation modifications, linker modifications, and functional moieties including, e.g., Fc fragments, serum albumin, and / or polyethylene glycol (PEG) groups, which can improve efficacy, therapeutic index, half-life, and ease of manufacture while maintaining functionality and specificity in the treatment of diseases such as cancer.

The application discloses a method for modifying pH sensitivity of an antibody based on yeast display. A degenerate codon VAM (coding H, E, D, K, N, Q) is used to construct a yeast display library for at least two region combinations in LCDR1, HCDR1 and HCDR3, and 1-2 mutations are introduced into each CDR region, taking the antibody to be modified as a template. The library is transformed into Saccharomyces cerevisiae EBY100 to induce expression, and fast dissociation clones are enriched through four rounds of flow sorting (including pH 7.4 binding, pH 6.0 non-binding and'saturated binding-acid dissociation-neutral re-binding' screening). The obtained antibody has a KD ratio at pH 5.8 to pH 7.4 of up to 674.46, an expression amount of up to 263.3 mg / L, excellent physicochemical properties, and can enhance the curative effect of antibody conjugated drugs and improve the therapeutic index.

This invention relates to the field of rat coronary heart disease complicated with depression treatment and intervention technology, and discloses a rat coronary heart disease complicated with depression treatment and intervention system, including a multidimensional acquisition module and an intelligent intervention module. The system acquires experimental data, metabolomics data, and efficacy data of intervention programs from all rats through the multidimensional acquisition module, and classifies them into datasets. The intelligent intervention module calculates a disease index based on the multidimensional data, accurately quantifies the severity of symptoms, and achieves dual correlation verification between metabolic mechanisms and pathological phenotypes. The multidimensional correlation has high accuracy. The intelligent intervention module evaluates the treatment effect of each rat after receiving different intervention programs, generates a treatment index, and assesses the population coverage of each intervention program's effect, generating an effectiveness index. It determines the symptom level and efficacy level of each rat, outputs corresponding evaluation results and intervention suggestions, and optimizes the intervention program through population data feedback. The intelligent intervention treatment effect is excellent.

The novel compound 3-(1-(2,3-dichloro-4-methoxyphenyl)ethyl)-1-methyl-1-(1,3,3-trimethylpiperidin-4-yl)urea monohydrochloride has high permeability, is able to cross the blood-brain barrier and shows consistent ghrelin agonist activity at the level of the central nervous system; the compound is effective in the treatment and / or prevention of medical conditions mediated by ghrelin receptors in the central nervous system. In particular, in experimental tests, the compound shows high efficacy in the treatment of neurotoxic injuries and has an effective neuroprotective action combination pattern at both central and peripheral levels. The compound is also useful in the treatment of diseases requiring a reduction in heart rate. The compound has pharmacological activity at low to moderate doses, thus showing a good therapeutic index.

This disclosure relates to novel GSPT1 degraders and the use of novel GSPT1 degraders. More specifically, this disclosure relates to a compound represented by formula I, or its stereoisomer, hydrate, solvate, or pharmaceutically acceptable salt, a pharmaceutical composition containing the same for treating disorders of uncontrolled cell proliferation, and a method for treating disorders of uncontrolled cell proliferation by administering the same to a mammal. The compounds relating to this disclosure exhibit high selectivity and sustained degrading activity for GSPT1, excellent pH stability, and low cytotoxicity to normal cells, and therefore have excellent anticancer efficacy and a high therapeutic index. In addition, the compounds relating to this disclosure may exhibit excellent anticancer activity against cancers exhibiting a neuroendocrine phenotype, such as small cell lung cancer (SCLC), neuroendocrine pulmonary cancer (NEC), and neuroendocrine prostate cancer (NEPC).

This invention discloses a copper dicyclopentyl dithiocarbamate compound and its applications, relating to the field of pharmaceutical chemistry, with the molecular formula C0. 22 H 36 CuN2S4, with a central copper ion and two dicyclopentyl dithiocarbamate ligands coordinated via sulfur atoms to form a four-coordinate planar square structure, or its pharmaceutically acceptable salts, solvates, crystal forms, or hydrates. This invention utilizes a novel chemical entity of dicyclopentyl-substituted copper dithiocarbamate, leveraging the greater steric hindrance and lipophilicity advantages of its cyclopentyl structure, as well as its selective response to the high-copper microenvironment of cholangiocarcinoma. Furthermore, it exhibits strong targeting, achieving high enrichment in liver and cholangiocarcinoma tissues, broadening the therapeutic index. Simultaneously, by avoiding the inhibition of systemic ALDH2 activity, it eliminates the alcohol-like toxicity caused by acetaldehyde accumulation. Moreover, it does not cross the blood-brain barrier, exhibits no significant neurotoxicity or cardiotoxicity, is patient-friendly for those with renal insufficiency, and demonstrates high safety.

This invention discloses an iridium complex, its preparation method, and its application in the treatment of neuromas. The iridium complex has the following structure: The iridium complex of this invention is a near-infrared fluorescent iridium complex, which exhibits a strong photodynamic therapeutic effect on the mouse neuroma cell line (Neuro-2a cells). Under light irradiation, it strongly inhibits the growth and proliferation of mouse neuroma cells (IC50). 50 The concentration was 0.05 μM, while under dark conditions, its cytotoxicity was only 87.5 μM, and the phototherapy index (PI) was as high as 1750. This is of great significance for the research of metal drugs for the treatment of neuromas.

This invention discloses a near-infrared light-excited iridium complex, its preparation method, and its application in anti-breast cancer treatment, comprising the structure shown in formula (I): The complex of the present invention exhibits a strong inhibitory effect on the growth and proliferation of mouse breast cancer cells (IC50). 50 The concentration of the phototoxicity was 0.31 μM, while under dark conditions, its cytotoxicity was only 93.9 μM, and the phototherapy index (PI) was as high as 301. This is of great significance for the research of metal drugs for anti-tumor purposes such as breast cancer.

The application belongs to the technical field of biology, and discloses application of emodin-8-glucoside in preparation of a product for preventing and / or treating tangu virus infection; through in-vitro experiments using a recombinant duck tangu virus stably expressing EGFP, it is proved that emodin-8-glucoside can efficiently inhibit virus replication, and the half effective concentration (EC 50 ) thereof is as low as 1.935 μM, the half cytotoxicity concentration (CC 50 ) thereof is as high as 511.3 μM, the calculated therapeutic index (SI) is 264.24, and the compound has the outstanding characteristics of high efficiency and low toxicity, and is high in clinical application safety; through duck infection model experiments, it is proved that after treatment of emodin-8-glucoside, the virus load in the spleen of the infected duck can be extremely significantly reduced, and the reduction amplitude is as high as 99%, which indicates that emodin-8-glucoside can effectively inhibit the replication of DTMUV in the duck body, and has a definite therapeutic effect; meanwhile, the application also provides a medicine containing emodin-8-glucoside.

The present invention relates to novel anti-CD3 antibodies with improved properties. These antibodies can be used on their own, but also can be "split" for use with a pair of recombinant binding molecules. Such molecules conditionally form active effector domains upon co-localization on tumor cells. Specifically, affinity optimizations between the two counterparts provide advantageous properties, such as increased therapeutic index and reduced target-mediated drug-disposition.

The present disclosure provides modified bispecific molecules that target (a) tumor-specific mutant peptides or mutant-associated neoantigens (MANAs) presented by human leukocyte antigens (HLAs) on the surface of target cancer cells; and (b) surface proteins (e.g., CD3) expressed on effector immune cells (e.g., T cells), and methods of using the same for cell therapy to diagnose, prevent, and / or treat human diseases, including cancer. The bispecific molecules are modified to additionally comprise domain orientation modifications, linker modifications, and functional moieties, including, for example, Fc fragments, serum albumin, and / or polyethylene glycol (PEG) groups, that can improve their potency, therapeutic index, half-life, and manufacturability, while maintaining functionality and specificity in the treatment of diseases, such as cancer.