144 results about "Camptothecin" patented technology

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

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.

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.

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 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.

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 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.

This invention relates to biomimetic mineralized exosomes for programmed drug penetration in tumors that inhibit cell burial, along with their preparation method and applications. Belonging to the field of novel excipients and dosage forms for pharmaceutical formulations, this invention co-loads the small-molecule chemotherapeutic drugs 10-hydroxycamptothecin and banoanthraquinone into exosomes. Then, through a biomimetic mineralization strategy, aTIM-4 is organically combined with mineralized calcium phosphate particles to obtain biomimetic mineralized exosomes. Under the acidic response of the tumor microenvironment, the calcium phosphate shell dissolves, and the exosome nucleus enters the tumor cells, inducing cell death and generating apoptotic bodies. This programmatically delivers the drug, delivering banoanthraquinone deep into the tumor. Simultaneously, the released aTIM-4 inhibits the cell burial of tumor-associated macrophages, amplifying the programmed drug penetration based on apoptotic bodies. This invention provides a new strategy and more options for overcoming the bottleneck of nanomedicine penetration in tumors, meeting the urgent clinical need for highly effective chemotherapeutic agents.

The present disclosure relates to a Camptothecin compound having anti-tumor activity, a preparation method therefor, and an application thereof. Specifically, the present disclosure relates to a compound as shown below or a pharmaceutically acceptable form thereof, a pharmaceutical composition thereof, a preparation method therefor, and a use thereof. The compound can be used as a drug for treating diseases in abnormal cell proliferation,

Provided is a method for preparing a camptothecin conjugate. The new method for preparing a camptothecin conjugate exhibits one or more effects selected from the group consisting of a high yield, a simple purification process, low impurities, suitability for industrial production, and high stability.

The invention relates to the field of medicines, and provides a series of camptothecin-7-ethylamine derivatives and a preparation method and application thereof, or pharmaceutically acceptable salts, stereoisomers or prodrugs thereof, and the camptothecin-7-ethylamine derivatives have a structure as shown in a formula (1).

The invention provides a paclitaxel precursor nano-drug as well as a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. Comprising a paclitaxel dimer prodrug and 7-ethyl10-hydroxy-camptothecin loaded on the paclitaxel dimer prodrug. According to the invention, a paclitaxel dimer prodrug is used as a self-assembly monomer to construct a PTX-SN38 synergistic treatment nano system, and the system has the advantages of dispersibility in water, biocompatibility, tumor specific response, synergistic treatment and the like, and can effectively solve the limitation of paclitaxel and SN38 in anti-tumor treatment.

This invention provides a class of D-configuration oncolytic peptide-camptothecin conjugates, their preparation methods, and applications, belonging to the fields of peptide preparation and biomedical technology. The steps are as follows: D-configuration peptides are synthesized using a solid-phase peptide synthesis method based on 9-fluorenemethoxycarbonyl. Then, the synthesized D-configuration peptides are covalently linked to a small molecule antitumor drug via a linker group. The D-configuration oncolytic peptide-camptothecin conjugates are obtained through peptide cleavage, separation and purification, and freeze-drying. The D-configuration oncolytic peptide-camptothecin conjugates significantly improve the solubility of camptothecin, exhibiting advantages such as high enzymatic stability, long half-life, and stronger inhibitory effect on tumor cell proliferation. Furthermore, this invention enables spatiotemporal monitoring of the release of camptothecin conjugates, thus possessing good practical application value.

The invention provides a GSH (glutathione) reduction response type targeted nano-drug based on chondroitin sulfate as well as a preparation method and application of the GSH reduction response type targeted nano-drug. Chondroitin sulfate with CD44 receptor targeting ability and an anti-cancer drug camptothecin are covalently linked through a disulfide bond sensitive to GSH, and the constructed novel targeting nano-drug can accurately recognize human colorectal cancer tumor cells highly expressed by a CD44 receptor in a targeting manner. Meanwhile, the high-concentration glutathione at the tumor site can oxidize and reduce the disulfide bond to cause the fracture of AC-CPT NPs, so that the effective release of the camptothecin medicine at the tumor site is realized, and the anti-tumor effect is further enhanced. The reduction response type targeting nano-drug prepared by the invention solves the problems of poor targeting and biological solubility and limited treatment effect of the traditional anti-cancer drug camptothecin, and provides an innovative strategy for realizing accurate targeting and efficient treatment of cancers.

The invention relates to the technical field of textile processing, and discloses a production process for improving the stain-resistant function of a sweater, the process comprises five steps of pretreatment, stain-resistant solution preparation, dipping treatment, pre-drying curing and finished product treatment: firstly, dedusting, washing, dehydrating and pre-drying a sweater blank to remove impurities; mixing and stirring the modified camptothecin, fatty alcohol-polyoxyethylene ether, water, ethylene glycol and perfluorohexyl ethyl alcohol according to a specific weight part ratio to prepare a stain-resistant solution; then, the pretreated blank is soaked in a stain-resistant solution, and stain-resistant components are fully permeated through constant-temperature soaking, regular stirring and ultrasonic treatment; then, through gradient heating pre-drying and curing, the stain-resistant components are firmly attached to the surfaces of the fibers; and finally, performing finished product treatment such as cooling and shaping to obtain the stain-resistant sweater. The finished sweater produced by the process has a lasting stain-resistant effect, can keep the original properties such as warm keeping and softness of natural fibers, and solves the problem that the traditional sweater is easy to stain.

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.

The application discloses a kind of endoplasmic reticulum of tumor cell can be targeted N -(2-hydroxypropyl) methacrylamide (HPMA) polymer-drug conjugate. The chemotherapeutic drug carried by the HPMA polymer is at least one of doxorubicin, epirubicin, pirarubicin, cisplatin, oxaliplatin, camptothecin, paclitaxel, gemcitabine, methotrexate, vinblastine, mitoxantrone, irinotecan, and the linker for connecting the drug and the HPMA polymer is at least one of hydrazone bond, amide bond, ester bond, disulfide bond, and ketosulfenyl bond. The HPMA polymer-drug conjugate targets the drug to the endoplasmic reticulum through receptor-ligand interaction, can cause severe endoplasmic reticulum stress, thereby transporting a large amount of calnexin to the tumor cell membrane surface, greatly improving the immunogenicity of tumor cells, and promoting tumor immunotherapy.

Provided herein are compounds, including compounds of Formula (I''), (I'), and (I), and a pharmaceutically acceptable salts thereof, which comprise a fibroblast activating protein (FAP)-cleavable moiety and are capable of delivering a camptothecin to FAP-expressing tissues (eg., cancers). Also provided herein are pharmaceutical compositions and kits comprising the same, as well as methods of using the same.

Antibody-drug conjugates (ADCs) comprising an antibody construct that binds specifically binds human folate receptor alpha (FRα) (an anti-FRα antibody construct) conjugated to a camptothecin analogue of Formula (I). The ADCs are useful as therapeutics, in particular in the treatment of cancer.

The present disclosure provides antibody-drug conjugate (ADC) structures where the antibody-drug conjugate includes a camptothecine or a camptothecine derivative linked to a polypeptide (e.g., an antibody) through a linker. In addition, the disclosure also encompasses compounds and methods for production of such conjugates, as well as methods of using the conjugates.

The invention discloses a camptothecin compound and a conjugate thereof. The invention provides a compound as shown in a formula I, a solvate of the compound, a pharmaceutically acceptable salt of the compound or a solvate of the pharmaceutically acceptable salt of the compound. The camptothecin compound disclosed by the invention has better anti-tumor activity, and the antibody drug conjugate prepared based on the camptothecin compound also has better anti-tumor activity.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to an alkaloid compound as a novel topoisomerase I inhibitor and a preparation method and application thereof. The alkaloid compound with a brand new structure is separated from the traditional Chinese medicine peganum harmala. Researches show that the alkaloid compound has very significant topoisomerase I inhibitory activity, and the topoisomerase I inhibitory activity is stronger than that of a positive drug camptothecin. The topoisomerase I plays a key role in DNA replication and division of tumor cells, so that proliferation of cancer cells can be blocked by inhibiting the topoisomerase I. Therefore, when the compound is used as an effective component for preparing the anti-cancer drug, a new material basis can be provided for drug research and development, the curative effect is improved, and side effects are reduced; the compound can also be used as a lead compound, high-activity anti-cancer molecules are derived through structural optimization, and the compound has important application value in the field of cancer treatment.

The application relates to a kind of SN38-fatty alcohol prodrugs and its self-assembly nanoparticles and application, belong to the field of new excipients and new dosage forms of pharmaceutical preparations, and relates to a kind of 7-ethyl-10-hydroxy camptothecin prodrug antitumor preparation, specifically to the construction of SN38-fatty alcohol prodrug and its self-assembly nanoparticles containing the prodrug, and its application as a drug delivery system in the preparation of antitumor drugs.The structure general formula (I) of SN38-fatty alcohol prodrug or its pharmaceutically acceptable salt is as follows: wherein, n, R, X are described in the claims and the specification.The SN38-fatty alcohol prodrug of the application can be self-assembled into nanoparticles, can effectively improve curative effect, reduce its toxic side effect.