312 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.

Provided are a camptothecin compound, an antibody drug conjugate, and a preparation method therefor and the use thereof. Specifically provided is a camptothecin compound as represented by formula (K) or a pharmaceutically acceptable salt thereof. The provided camptothecin compound and the antibody drug conjugate thereof have a good cytotoxic activity and can inhibit the proliferation of tumor cells.

A series of novel anti-B7-H3 antibodies. The antibodies have high affinity to B7-H3 and have stable structures. Also provided is an antibody drug conjugate prepared by using said antibody. The antibody drug conjugate uses a camptothecin compound having a specific structure as a toxic molecule, has significant tumor inhibition activity, and has a bystander killing effect.

The invention provides Motixazotide-camptothecin conjugates as well as a preparation method and application of the Motixazotide-camptothecin conjugates, and belongs to the fields of polypeptide preparation and biological medicines. According to the invention, a series of novel Motixafortide-camptothecin conjugates are synthesized, and the Motixafortide-camptothecin conjugates are formed by connecting Motixafortide with different quantities of camptothecin through a linking group. An anti-tumor proliferation and migration experiment, cellular uptake and an aging curve show that the Motixazotide-camptothecin conjugate can improve the membrane penetrability and the anti-tumor activity of the camptothecin, improve the selectivity of the camptothecin to tumor cells and reduce the toxicity of the camptothecin to normal cells. Meanwhile, the solubility of the Motixazotide-camptothecin conjugate is more than 1000 times of that of the camptothecin. In addition, according to the intramolecular self-quenching Motixazotide-camptothecin conjugate prepared by the preparation method disclosed by the invention, the real-time monitoring on the release condition of the camptothecin anti-tumor drugs is realized. Therefore, the method has good practical application value.

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 invention provides a Chinese herbal medicine composition for improving immunity as well as a preparation method and application thereof, and belongs to the technical field of medicines. The preparation method comprises the following steps: fermenting rhizoma anemarrhenae, poria cocos, rhizoma polygonati and fructus lycii to prepare Chinese herbal medicine selenium / germanium-rich polysaccharide, carrying out carboxylation modification on the Chinese herbal medicine selenium / germanium-rich polysaccharide and phycobiliprotein to prepare a Chinese herbal medicine selenium / germanium-rich polysaccharide-phycobiliprotein compound, and dissolving bacterial sludge in the fermentation process with helicase to prepare a bacteria-dissolving product; and uniformly stirring and mixing with the Chinese herbal medicine selenium / germanium-rich polysaccharide-phycobiliprotein compound, berberine and camptothecin to prepare the Chinese herbal medicine composition for improving immunity. The prepared Chinese herbal medicine composition capable of improving immunity contains rich glycoprotein and organic selenium / germanium compounds, has the effects of consolidating body resistance and strengthening yang, has the advantages of good sterilization, oxidation resistance, inflammation resistance, virus resistance and tumor resistance, no toxicity, high bioavailability, easiness in absorption and the like, is high in patient compliance and has a wide application prospect.

The invention discloses a camptothecin micromolecule, an antibody drug conjugate thereof, a preparation method and an application. The invention provides a camptothecin micromolecule as shown in a formula I or a pharmaceutically acceptable salt thereof. The camptothecin micromolecule provided by the invention and the antibody drug conjugate thereof have good cytotoxic activity and can inhibit proliferation of tumor cells. # imgabs0 #

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 present invention relates to antibody conjugates which are particularly suitable for targeting CEA-expressing cells, in particular tumor cells. An antibody conjugate according to the present invention has the structure (1): AB-[(L6) b-{Z-L-D} x] y (1) wherein AB is an antibody capable of targeting a tumor expressing CEA; 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 hemiphyllum, a KSP inhibitor, a TLR agonist, an indolo-benzodiazepine # imgabs 0 # dimer or a pyrrolo-benzodiazepine # imgabs 1 # dimer (PBD), and analogs or prodrugs 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 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-trifluoromethoxy camptothecin compounds and application of the 10-trifluoromethoxy camptothecin compounds in antitumor drugs. The structural formula of the compounds is shown in the specification. In-vitro cytotoxic activity screening results show that the 10-trifluoromethoxy camptothecin compound has broad-spectrum anti-tumor activity, and shows relatively strong inhibitory activity on human liver cancer cells (HepG2), human non-small cell lung cancer cells (A549), human colon cancer cells (SW480), human bile duct cancer cells (QBC939), human breast cancer cells (MCF-7), human pancreatic cancer cells (PANC-1) and human pancreatic cancer cells (BxPC-3). The compound 10-trifluoromethoxy camptothecin I and the compound 7-ethyl-10-trifluoromethoxy camptothecin II have a relatively strong inhibition effect on the detected seven tumor cell lines, and the IC50 (half maximal inhibitory concentration) values of the compound 10-trifluoromethoxy camptothecin I and the compound 7-ethyl-10-trifluoromethoxy camptothecin II are respectively 0.913 to 0.0661 mu M and 4.932 to 0.0578 mu M, which are obviously superior to those of a contrast drug topotecan. Wherein the compound I and the compound II show the strongest inhibitory activity on a BxPC-3 cell line, and the IC50 values of the compound I and the compound II are 0.0661 + / -0.0065 [mu] M and 0.0578 + / -0.0043 [mu] M respectively. Therefore, the 10-trifluoromethoxy camptothecin compound is expected to be developed into a novel antitumor drug. # imgabs0 #

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.

A camptothecin small molecule and an antibody drug conjugate thereof, a preparation method therefor and the use thereof. Provided is a camptothecin small molecule as shown in formula I or a pharmaceutically acceptable salt thereof. The provided camptothecin small molecule and the antibody drug conjugate thereof have a good cytotoxic activity, and can inhibit the proliferation of tumor cells.

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 invention relates to a preparation method of bovine serum albumin-loaded camptothecin nanoparticles, which is characterized in that BSA (bovine serum albumin) is modified by PEG (polyethylene glycol), so that the biocompatibility and the stability of the nanoparticles are enhanced, PEG-BSA-CPT-NPs is prepared, and the water solubility of CPT is increased by nearly 10 times. A freeze drying-ultrasonic method is adopted to replace high-pressure homogenization to realize an emulsification process, so that the defect that the secondary and tertiary structures of the protein are changed due to high-pressure homogenization to cause expansion or denaturation of the protein is overcome. In addition, a freeze-drying step is introduced on the basis of a traditional ultrasonic emulsification method, the drug-loaded nanoparticles are freeze-dried into powder, and then ultrasonic treatment is performed. The particle size of the prepared PEG-BSA-CPT-NPs nanoparticle meets the standard of the ideal size of a nano-drug, the nanoparticle can penetrate through a tumor microenvironment and is prevented from being rapidly removed, and the anti-tumor activity of CPT is improved.

The invention provides a series of novel anti-B7-H3 antibodies. The antibody has high affinity to B7-H3 and is stable in structure. The invention further provides an antibody drug conjugate prepared from the antibody, and the antibody drug conjugate takes the camptothecin compound with a specific structure as a toxic molecule, has remarkable tumor inhibition activity and has a bystander killing effect.

Provided is an antibody-drug conjugate, specifically comprising a connected therapeutic antibody portion, an intermediate linker portion and a cytotoxic drug portion, wherein the therapeutic antibody portion is an antibody against the HER2 target, the cytotoxic drug portion is a camptothecin-type topoisomerase I inhibitor, and the cytotoxic drug portion or the linker-cytotoxic drug portion is modified by deuterium substitution. The antibody-drug conjugate can be used for the prevention or treatment of cancer. #imgabs0#

Antibody conjugates with camptothecin compounds are described, with methods of use and preparations.

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.