227 results about "Camptothecin" patented technology

The invention relates to the field of antitumor drugs, in particular to a pharmaceutical composition of a KRAS G12C inhibitor and camptothecin and application of the pharmaceutical composition. The camptothecin and the KRAS G12C inhibitor are combined to play a synergistic effect, a DNA damage repair pathway is inhibited, a better inhibition effect is generated on tumor cells containing KRAS G12C mutation, the dosage required for achieving the same anti-tumor effect is greatly reduced, and the medication safety is improved.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to camptothecin compounds and a preparation method thereof. The compound shows good tumor inhibition activity and can be used as a cancer therapeutic agent.

The present invention relates to camptothecin compounds with antitumor activity, their preparation methods and their applications.Specifically, the present invention relates to the following compounds or their pharma- ceutically acceptable forms, their pharmaceutical compositions, their preparation methods and their uses.The compounds can be used as drugs to treat diseases in abnormal cell proliferation. JPEG2024506819000283.jpg44149

The invention provides a camptothecin prodrug. The camptothecin prodrug provided by the invention has higher drug retention in the liposome and better stability, and the prodrug liposome can maintain long-time plasma concentration in plasma. In-vitro characterization of the camptothecin prodrug liposome shows that the camptothecin prodrug liposome has higher encapsulation efficiency, drug loading capacity and stability, and can achieve a slow release effect in plasma; the experimental result on the cellular level shows that the compound has higher cellular uptake rate; in-vivo experiments prove that the compound has a better tumor accumulation effect and antitumor activity, can tolerate a higher dosage, and has higher biological safety.

Described is an antibody-drug conjugate (ADC) having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, preferably a camptothecin cytotoxic molecule which is cell-permeable; and as a second payload a topoisomerase I inhibitor which is not cell-permeable, preferably a camptothecin cytotoxic molecule which is not cell-permeable. Moreover, described is a pharmaceutical composition comprising said ADC and at least one pharmaceutically acceptable ingredient. Further, described is an ADC for use in a method of treating a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease.

Described is an antibody-drug conjugate (ADC) having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, e.g., a camptothecin cytotoxic molecule which is cell-permeable; as a second payload a topoisomerase I inhibitor which is not cell-permeable, e..g., a camptothecin cytotoxic molecule which is not cell-permeable; and as a as a third payload a toxin or a cytotoxin, e.g., an auristatin such asMMAE (Monomethyl auristatin E). Moreover, described is a pharmaceutical composition comprising said ADC and at least one pharmaceutically acceptable ingredient. Further, described method of treating a patient suffering from, being at risk of developing, and / or being diagnosed for a neoplastic disease.

The invention relates to preparation of 10-hydroxycamptothecine modified polypeptide and a research on cytotoxicity of the 10-hydroxycamptothecine modified polypeptide. The method comprises the following steps: synthesizing SA-7 polypeptide by adopting an F-moc solid-phase synthesis method, and combining the SA-7 polypeptide with 10-hydroxycamptothecine through chemical coupling reaction to obtain the SA-7-HCPT compound. C18 reversed-phase high performance liquid chromatography (RP-HPLC) is used for purification, and the molecular weight is identified to be 1898Da by using mass spectrum. A further cytotoxicity test shows that the SA-7-HCPT shows relatively strong anticancer activity to HepG2, and the toxicity of the SA-7-HCPT to HepG2 is remarkably superior to that of 10-HCPT to HepG2. Meanwhile, the toxicity of SA-7-HCPT to normal liver cells LO2 is relatively low, and the SA-7-HCPT shows good selectivity. Therefore, the SA-7-HCPT has a relatively good clinical application prospect.

To provide camptothecin compounds and their conjugates with novel structures, improved efficacy and improved safety.SOLUTION: The present invention provides a compound having the structure of the upper formula in the figure, or a pharmaceutically acceptable salt, ester, stereoisomer, polymorph, solvate, nitrogen oxide, isotope-labeled product, metabolite or prodrug thereof. In the formula, R1 and R2 are each hydrogen, halogen, C1-6 alkyl, C1-6 alkoxyl, or the like, or are connected with adjacent carbon atoms to form a 5- to 6-membered oxygen-containing heterocyclic ring; R3 is hydrogen or is connected with an ortho-carbon atom of R1 to form a 6-membered carbocyclic ring; and A is selected from one of the lower two formulas in the figure.SELECTED DRAWING: None

Disclosed are a deuterated camptothecin compound represented by formula II and a pharmaceutically acceptable salt thereof, a preparation method thereof, a pharmaceutical composition containing the deuterated camptothecin compound or the pharmaceutically acceptable salt thereof, and uses thereof in the treatment of tumor-related diseases. The deuterated camptothecin compound has excellent pharmaceutical activity and pharmacokinetic characteristics, and has reduced in-vivo toxicity and improved in-vivo safety.

The invention discloses a GRB2 small-molecule inhibitor as well as a preparation method and application thereof. The preparation method comprises the following steps: carrying out structural modification on a phenolic hydroxyl group of hydroxycamptothecin, and carrying out a reaction on 3-(2-bromoethyl)-3-(butyl-3-alkyn-1-yl)-3H-diaziridine and hydroxycamptothecin to obtain the GRB2 small-molecule inhibitor, and naming a new compound as HCPT-pt. Experiments prove that the compound HCPT-pt is a novel GRB2 small-molecule inhibitor, the esophageal cancer cell killing capacity is higher than that of hydroxycamptothecin, and the compound HCPT-pt can be used as a medicine for widely treating tumor diseases.

To provide camptothecin compounds and their conjugates with novel structures, improved efficacy and improved safety.SOLUTION: The present invention provides a compound having the structure of the upper formula in the figure, or a pharmaceutically acceptable salt, ester, stereoisomer, polymorph, solvate, nitrogen oxide, isotope-labeled product, metabolite or prodrug thereof. In the formula, R1 and R2 are each hydrogen, halogen, C1-6 alkyl, C1-6 alkoxyl, or the like, or are connected with adjacent carbon atoms to form a 5- to 6-membered oxygen-containing heterocyclic ring; R3 is hydrogen or is connected with an ortho-carbon atom of R1 to form a 6-membered carbocyclic ring; and A is selected from one of the lower two formulas in the figure.SELECTED DRAWING: None

The present invention relates to antibody conjugates which are particularly suitable for targeting cells expressing PTK7, in particular tumor cells. An antibody conjugate according to the present invention has structure (1): AB-[(L6) b-{Z-L-D} x] y (1) wherein AB is an antibody capable of targeting a tumor expressing PTK7; l is a joint connecting Z to D; z is a linking group; l6 is-GlcNAc (Fuc) w-(G) j-S-(L7) w '-wherein G is a monosaccharide, j is an integer in the range of 0 to 10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine, and Fuc is fucose, w is 0 or 1, w' is 0, 1 or 2, and L7 is-N (H) C (O) CH2-,-N (H) C (O) CF2-or-CH2-; d is selected from the group consisting of an anthracycline, a camptothecin, a tubulysin, an endiyne, an amanitine, a duocarmycin, a maytansinoid, an aurestatin, eribulin, a BCL-XL inhibitor, a miscanthus semiaquilaria, a KSP inhibitor, a TLR agonist, an indolo-benzodiazepine dimer or a pyrrolo-benzodiazepine dimer (PBD), and an analog or prodrug thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further relates to a method for preparing said antibody conjugate of structure (1) and to the use of said antibody conjugate of structure (1).

The invention relates to an adipose-derived stem cell and exosome composition for mucosal inflammation and an application of the adipose-derived stem cell and exosome composition. The composition is composed of a hybrid nano-vesicle and a pulsatilla chinensis exosome compound in a mass ratio of 1: 1. The hybrid nanovesicles are prepared by fusing adipose-derived stem cell exosomes and lipidosome and modifying honey polysaccharide, and the pulsatilla chinensis exosome compound is loaded with interleukin 23 peptidomimetic, polyethylene glycol, black scale quantum dots and camptothecin. The composition has the functions of efficient anti-inflammation, immunoregulation, precise targeting and tissue repair, and meanwhile, the curative effect is enhanced through photo-thermal synergistic treatment. The preparation method comprises the steps of exosome extraction by a density gradient centrifugation method, liposome fusion and surface modification. The composition is suitable for treating mucosal inflammation such as inflammatory bowel disease and oral mucositis, has the advantages of high stability, good biocompatibility and the like, and provides a safe and effective novel treatment strategy for clinic.

The invention discloses a novel cleavable linker compound shown as a formula (1) and pharmaceutically acceptable salts, solvates, polymorphs or isomers of the novel cleavable linker compound. The novel cleavable linker compound can be used for a prodrug delivery system. The invention also provides an albumin or antibody covalent binding camptothecin derivative prodrug compound formula (J) and a camptothecin derivative prodrug compound formula (L) as well as pharmaceutically acceptable salts, solvates, polymorphs or isomers of the prodrug compound formula (J) and the pharmaceutically acceptable salts, solvates, polymorphs or isomers of the prodrug compound formula (L). The invention also provides a synthesis method of the compound and a preparation method of the compound in an enzyme release prodrug system. The invention also provides an application of the compound in preparation of antitumor drugs, and an application in preparation of albumin combined antitumor drugs or antibody-drug conjugates. The invention innovatively provides that a trigger fragment in the compound is connected to a novel linker through p-hydroxyl or p-amino, an active drug is connected to the novel linker through a hydroxyl part of the active drug, and a modified fragment is connected to the novel linker through amino. The method has a wide application prospect.

Provided herein are Camptothecin Conjugates, Camptothecin-Linker Compounds, Camptothecin Compounds, intermediates thereof, and method of preparing the same. Also provided herein are methods of treating cancer and autoimmune diseases with the Conjugates described herein.

A camptothecin conjugate compound and a preparation method therefor. The camptothecin compound has an excellent pharmacological activity and kinetic characteristics, and is suitable for preparing a drug for treating tumor-related diseases.

A camptothecin compound and a conjugate thereof, or a tautomer thereof, an enantiomer thereof, a diastereomer thereof, or a mixture form thereof, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutical composition thereof, a preparation method therefor, and use thereof. The compound and the conjugate can be used for treating proliferative diseases related to abnormal cell activity.

The present invention belongs to the field of biomedical materials and specifically relates to anti-tumor nanoparticles, their preparation methods, and applications. The present invention claims protection for an anti-tumor nanoparticle comprising compound PTe N25, wherein the nanoparticles are simultaneously encapsulated with a camptothecin compound and compound PTe N25 using a phospholipid. The structural formula of compound PTe N25 is: #imgabs0# The present invention utilizes cRGD and camptothecin compounds in conjunction with an organic conjugated polymer material to prepare a dual-targeted chemotherapy-photothermal therapy combined treatment system. This system achieves cRGD-targeted recognition of cancer cells, controlled drug release responsive to spatiotemporal light dual stimulation in the context of a diseased environment, and integrated chemotherapy and photothermal therapy synergistic treatment, significantly reducing drug toxicity and side effects while maintaining anti-tumor efficacy.

The invention provides a sensitizing camptothecin drug anti-tumor combined drug composition and application thereof, and particularly relates to application of an apigenin and camptothecin drug composition in preparation of anti-tumor drugs. A natural dietary supplement and an anti-tumor chemotherapeutic drug are creatively combined, a colorectal cancer in-vitro cell model is utilized to prove that the apigenin has the anti-tumor effect of sensitizing camptothecin drugs, the apigenin and the low-dose camptothecin drugs can activate a PI3K-AKT pathway and a dsDNA-cGAS-STING pathway, tumor immunogenic death is induced, and the apigenin has the anti-tumor effect. And the anti-tumor immune response is activated. The invention not only has the effects of reducing toxicity and enhancing efficacy on clinically applied camptothecin medicines, but also provides a new strategy for sensitizing colorectal cancer immunotherapy.

The invention provides a cyclodextrin medicine compound as well as a preparation method and application thereof, and belongs to the technical field of medicines. The preparation method comprises the following steps: performing hydroxylation modification on beta-cyclodextrin to prepare hydroxypropyl cyclodextrin, respectively embedding camptothecin, kushenin and bufalin, then performing spray drying with graphene oxide to prepare an embedded compound, depositing Ni-doped ferroferric oxide on the surface, and further performing folic acid modification to prepare the cyclodextrin medicine compound. The drug is conveyed to a tumor site through magnetic targeting, and the drug is combined with a receptor of tumor cells through active transportation of folic acid, so that the drug release precision is greatly improved, the drug has an extremely good treatment effect at a relatively low concentration, the adverse reaction of a patient is reduced, the compliance is improved, and the curative effect of the drug is improved. The medication cost is reduced, the bioavailability of the medicine is improved, and the application prospect is wide.

The invention provides a planting method for promoting synthesis of camptothecin and derivatives thereof from nothapodytes pittosporoides. The planting method comprises the following steps: planting a plurality of nothapodytes pittosporoides trees in a planting field; organic fertilizer is applied to the multiple planted nothapodytes pittosporoides trees every first preset time; the planted nothapodytes pittosporoides trees are soaked with cold water for several days, and temperature and water stress is carried out; removing the nothapodytes nothapodytes which do not survive after water stress; introducing microorganisms every second preset time to adjust rhizosphere microorganisms of the nothapodytes pittosporoides trees so as to carry out microorganism stress; watering is stopped in autumn, so that the survival nothapodytes nothapodytes trees are subjected to sunlight stress, and the survival nothapodytes nothapodytes trees enter the sunlight stress period; in the sunlight stress period, synthesis of terpene indole alkaloid of rhizosphere microorganisms is activated, and synthesis of camptothecin and derivatives of camptothecin from nothapodytes pittosporoides is promoted; wherein except for the sunlight stress period, the environment temperature of the planting field is kept at 5 DEG C or above, and the environment humidity is kept at 63%-78%.

The invention relates to an antibody-drug conjugate formed by an anti-human DLL3 antibody and a camptothecin drug, and a medical application of the antibody-drug conjugate. The present invention also relates to linker-drug conjugates that can be conjugated with antibodies to form antibody drug conjugates.

Provided is an antibody-drug conjugate (ADC) having a drug-linker conjugate (A) linked thereto and a preparation method therefor, including a combination of a camptothecin-based drug that degrades DDX5 protein with a DAR of 4 or more and either (i) an acid-sensitive linker or (ii) an enzyme-sensitive linker. The antibody-drug conjugate is designed to increase the therapeutic index of the camptotechin-based drug payload while suppressing the non-selective uptake of the camptothecin-based drug and / or ADC released from apoptotic cells. The ADC is designed and / or synthesized so that two types of drug-linker conjugates including: a drug-linker conjugate (A) composed of a combination of a camptothecin-based drug that degrades DDX5 protein with a DAR of 4 or more and either (i) an acid-sensitive linker or (ii) an enzyme-sensitive linker; and a drug-linker conjugate (B) composed of a combination of a non-camptothecin cytotoxic drug and an enzyme-sensitive linker are each linked to a single antibody.

The invention discloses preparation of supramolecular nanoparticles self-assembled by polypeptide coupling drugs with stimulation responsiveness and application of the supramolecular nanoparticles in brain tumors. The supramolecular nanoparticles comprise a requinomod analogue and a camptothecin analogue. A requinomod analogue and a camptothecin analogue are connected to a brain targeting peptide through a sensitive peptide, and are further self-assembled to form supramolecular nanoparticles, so that the brain targeting ability and intracerebral retention efficiency of the drug are improved. The polypeptide coupled drug supramolecular nanoparticles provided by the invention show excellent capabilities of killing tumor cells and polarizing anti-inflammatory macrophages in vivo and in vitro, have a strong inhibition effect on brain tumors, and have huge clinical application value.

A camptothecin conjugate and a preparation method thereof. The camptothecin conjugate has excellent drug activity and kinetic characteristics, and is suitable for preparing a drug for treating tumor-related diseases.

The invention belongs to the field of pesticides, and particularly relates to a botanical weeding composition which comprises an active component A and an active component B, the active component A is paeonol or artesunate, the active component B is 7-ethyl camptothecin, and the mass ratio of the active component A to the active component B is (1: 10)-(10: 1). The botanical herbicidal composition has excellent herbicidal activity on barnyard grass, nutgrass flatsedge and sticktight due to the synergistic effect of the two components, and can be directly developed into a botanical herbicidal active component composition for preventing and controlling gramineae, nutgrass flatsedge and broadleaf weeds in farmland.

The invention provides an antibody drug conjugate which specifically comprises a therapeutic antibody part, an intermediate joint part and a cytotoxic drug part which are connected, the therapeutic antibody part is an antibody aiming at an HER2 target spot, and the cytotoxic drug part is a camptothecin topoisomerase I inhibitor. The cytotoxic drug part or the linker-cytotoxic drug part is subjected to deuterium-substituted modification. The antibody drug conjugate can be used for preventing or treating cancers. # imgabs0 #

The invention discloses an albumin coupling medicine as well as a preparation method and application thereof. The cathepsin B response type camptothecin albumin coupling drug is innovatively designed and synthesized by taking albumin as a carrier, the albumin coupling drug has good cathepsin B response drug release capability, efficient tumor targeted delivery of the drug is realized, camptothecin is responded and released in tumor cell lysosome, and the drug delivery efficiency is improved. The specific anti-tumor effect is achieved. The invention provides a regulation and control method in the aspects of preparation, drug loading capacity and in-vitro release of the albumin coupled drug, size effects in the aspects of cellular uptake, cytotoxicity, tumor targeting and retention are illustrated, and guidance is provided for designing an efficient and safe tumor drug delivery system.

To provide a pharmaceutical composition for cancer treatment which shows a synergistic cancer therapeutic effect when used in combination with an anti-tumor agent, and can be easily used as a cancer therapeutic agent and a combination therapeutic pharmaceutical.SOLUTION: Provided is a cancer treatment application of nanoparticles containing a slightly soluble camptothecin-based compound and a combined administration therapy with an anti-tumor agent using the application. In one embodiment, a combination pharmaceutical preparation for pancreatic cancer treatment contains: particles including SN-38(7-ethyl-10-hydroxycamptothecin), irinotecan, and an amphiphilic block copolymer made of a hydrophobic block and a hydrophilic block; and one or more kinds of anti-tumor agents selected from the group consisting of nab-paclitaxel as an active ingredient, the amphiphilic block copolymer being constituted of A-B or A-B-A block, (a) A is a hydrophilic polymer and is monomethoxypolyethylene, and (b) B is a hydrophobic polymer and is poly-D,L-lactide or a derivative thereof.SELECTED DRAWING: Figure 2