24 results about "Thalidomide" patented technology

The invention relates to the technical field of maternal and fetal medicine, in particular to a regional maternal and fetal medicine congenital structure anomaly risk assessment system based on big data. A regional feature quantification module; a risk assessment model module; an interpretability analysis module; and a streaming update module. According to the scheme, deep integration and unified representation of individual information and regional macroscopic attributes of pregnant and lying-in women are realized by constructing a multi-source heterogeneous data fusion and regional feature quantification mechanism. The system adopts a multi-protocol interface to access a hospital information system, an environment monitoring platform and a health statistics database, completes standardized cleaning and integrated processing of cross-domain data, and converts multi-dimensional indexes such as regional environment, medical resources, social economy and the like into low-dimensional dense feature vectors through a macroscopic data aggregation and ridge regression coding technology. The feature expression ability and the regional adaptability of the model are significantly enhanced, and effective data are provided for evaluating the risk of the innate structure anomaly of pregnant and lying-in women under different geographical backgrounds.

The invention provides maslinic acid PROTACs as well as a preparation method and application thereof, and belongs to the technical field of drug development. According to the invention, maslinic acid is taken as a POI ligand, lenalidomide and fluoro-thalidomide are taken as E3 ligands, and linker selects a PEG chain or an aliphatic chain, so that the anti-cancer activity of the compound is superior to that of maslinic acid, and the compound has a good potential application prospect in the aspect of anti-tumor treatment.

The present invention discloses a class of small molecule degraders targeting FGFR2, their pharmaceutical compositions and uses, belonging to the technical field of medicinal chemistry. The compounds provided by the present invention are bifunctional molecules that can serve as FGFR2 kinase inhibitors and also as FGFR2 protein degraders. This class of compounds uses the FGFR2 inhibitor TAS-120 as the target-binding part of the targeted protein for the protein degrader, and is coupled with thalidomide derivatives, hydrophobic tags and molecular glue fragments through different linkers to obtain bifunctional molecules that can both potently inhibit the kinase activity of FGFR2 and promote the degradation of FGFR2 protein. Moreover, they can also inhibit the proliferation of various cancer cells and have good potential for development as anti-tumor drugs.

The invention provides thalidomide and magnesium acetyltaurate nano eye medicine as well as a preparation method and application thereof. The preparation method comprises the following steps: S1, preparing thalidomide and magnesium acetyltaurate co-assembled nano particles; s2, preparing BHK21 cell membrane vesicles with high expression of transferrin; s3, the thalidomide and magnesium acetyltaurate co-assembled nanoparticles and the BHK21 cell membrane vesicles with high expression of transferrin are fully mixed and then subjected to ultrasonic treatment, and the thalidomide and magnesium acetyltaurate nano eye medicine is obtained. The thalidomide and magnesium acetyltaurate nano eye medicine has relatively high medicine concentration and has long-time medicine stability.

The invention provides SETDB1-targeting PROTAC as well as a preparation method and application thereof, and relates to the technical field of clinical medicine. The PROTAC comprises a nucleic acid aptamer capable of being specifically combined with SETDB1 protein, a connexon and a ligand for recruiting E3 ubiquitin ligase, wherein the ligand for recruiting the E3 ubiquitin ligase is thalidomide. The PROTAC can recruit the E3 ligase CRBN in cancer cells onto the SETDB1, and degrade the SETDB1 in a proteasome dependent manner. Therefore, the PROTAC can inhibit proliferation and migration of cancer cells; the killing effect of CD8 + T cells on cancer cells is enhanced, and the growth of the cancer cells is inhibited. Tests prove that the potential application of the PROTAC based on the aptamer in SETDB1 degradation in tumor cells provides a promising strategy for cancer treatment.

This invention discloses a chiral molecule sensing platform and detection method based on a chiral nanocone array and intelligent modeling. The chiral nanocone array sensing substrate includes a substrate and an Ag-SiO2-Au three-layer composite structure disposed on the substrate: an Ag layer, a SiO2 layer, and an Au layer; the Au layer is located outside the SiO2 layer, and the absolute value of the difference in the relative azimuth angle between the Au layer and the Ag layer is 90°. The chiral molecule sensing platform includes a chiral nanocone array sensing substrate, a spectral acquisition module, a signal processing module, and an intelligent modeling module. This invention solves the technical bottlenecks of traditional chiral sensing, such as weak response, poor analyte accessibility, low signal-to-noise ratio, and limited quantitative accuracy, achieving label-free identification of the chiral molecule thalidomide with 99% accuracy and 10... 2 -10 9 Precise quantification with a wide dynamic range (pg / mL) 2 With a value of ≥0.99, it is suitable for drug development, quality control and other scenarios, and has a wide range of application value.

A PAMAM-based protein degradation system and a method of preparation and use thereof are provided. The protein degradation system comprises: a silica nanoparticle core; and a poly(amidoamine) dendrimer (PAMAM) layer coated on a surface of the silica nanoparticle, wherein the PAMAM layer is linked via amide bonds to three small-molecule ligands: MDM2 protein ligand Idasanutlin, GLUT1 protein ligand Lavendustin B and E3 ubiquitin ligase ligand Thalidomide-NH—CH2—COOH. The nanoparticle protein degradation system cooperatively degrades MDM2 protein and GLUT1 protein. This cooperative degradation strategy not only effectively suppresses proliferation and energy metabolism of tumor cells, but also significantly enhances the stability of p53 protein. By restoring the normal function of p53 protein, tumor cell growth is further inhibited, providing a new strategy for cancer therapy.

The invention belongs to the technical field of biological medicines, and particularly relates to application of thalidomide in preparation of a prevention medicine or a treatment medicine for scar of conjunctival filtration vesicles after a glaucoma filtration operation. The thalidomide in the medicine disclosed by the invention can inhibit the cell activity of HTF in a concentration-dependent manner, prolong the survival time of filtration vesicles, and provide a medicine for resisting the scarring of the conjunctival filtration vesicles after the glaucoma filtration operation, which is satisfactory in curative effect and safe in application, so that the medicine can be used as a substitute for 5-FU and MMC.

The present disclosure relates in some aspects to methods, compositions and uses involving immunotherapies, such as adoptive cell therapy, e.g., T cell therapy, and an immunomodulatory compound, such as a structural or functional analog or derivative of thalidomide and / or an inhibitor of E3-ubiquitin ligase. The provided methods, compositions and uses include those for combination therapies involving the administration or use of one or more immunomodulatory compounds in conjunction with a T cell therapy, such as a genetically engineered T cell therapy involving cells engineered with a recombinant receptor, such as chimeric antigen receptor (CAR)-expressing T cells. Also provided are compositions, methods of administration to subjects, articles of manufacture and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, efficacy, persistence, expansion and / or proliferation of T cells for adoptive cell therapy or endogenous T cells recruited by immunotherapeutic agents.

A novel multi-fused-ring compound and a composition for preventing or treating multiple myeloma comprising the same as an active ingredient is described herein. The compound is a derivative synthesized from the natural compound ginsenoside as a starting material, and shows no cytotoxicity to normal hematopoietic stem cells, while exhibiting a significant killing effect on various multiple myeloma cell lines, indicating that it may be administered for a long period of time without side effects. In addition, the compound exhibits a significant synergistic effect when co-administered with the immunomodulator thalidomide or its analog lenalidomide, and thus may be useful as an efficient therapeutic agent or therapeutic aid agent composition for multiple myeloma, an incurable disease.

This invention discloses a method for identifying thalidomide R-type chiral molecules. The method includes the following steps: constructing a dataset, dividing the dataset into a training set and a test set according to a preset ratio; the dataset includes ECD spectra of thalidomide R-type chiral molecules, ECD spectra of diazepam molecules, ECD spectra of phenobarbital molecules, and corresponding label data; constructing a recognition model based on a CNN convolutional neural network, inputting the training set and test set into the recognition model for training and performance evaluation to obtain a trained recognition model; inputting the ECD spectrum of the thalidomide chiral molecule to be detected into the trained recognition model to obtain a recognition result, wherein the recognition result is thalidomide R-type chiral molecules or other molecules. This invention enables simple and rapid identification of thalidomide R-type chiral molecules.

The present invention provides a novel compound having a chromanone or its ring-opening form, phenylpropenone, as backbone and compositions for the preventing or treating multiple myeloma, comprising the same. The compounds of the invention exhibit significant killing effects against various multiple myeloma cell lines and show in vivo anti-cancer effects that exceed those of lenalidomide, a commercially available immunomodulator widely used in the treatment of multiple myeloma and myelodysplastic syndromes. In addition, the compounds of the invention exhibit a significant synergistic effect when co-administered with the thalidomide or its analog lenalidomide, and thus are useful as an efficient therapeutic agent or therapeutic aid agent composition for multiple myeloma which is an incurable disease.

The invention discloses a micromolecule degradation agent taking FGFR2 as a target spot as well as a pharmaceutical composition and application thereof, and belongs to the technical field of pharmaceutical chemistry. The compound provided by the invention can be used as an FGFR2 kinase inhibitor and also can be used as a bifunctional molecule of an FGFR2 protein degradation agent. According to the compound, an FGFR2 inhibitor TAS-120 is used as a target binding part of targeted protein of a protein degradation agent, a thalidomide derivative, a hydrophobic tag and a molecular film segment are coupled through different connectors, a bifunctional molecule which can strongly inhibit the activity of FGFR2 kinase and promote degradation of FGFR2 protein is obtained, proliferation of various cancer cells can be inhibited, and the compound has a good application prospect. The compound has good potential of being developed into anti-tumor drugs.

The invention discloses an enema preparation for treating ulcerative colitis, each liter of the enema preparation contains 0.01-2 g of thalidomide, 30-150 ml of dimethyl sulfoxide and 1-5 g of carbomer, and the enema preparation further comprises a regulator for regulating the pH value to 5.5-9.0 and deionized water. The components and the preparation method of the enema preparation are simple, the biocompatibility is high, the local concentration and retention time of thalidomide in the intestinal tract can be improved, the side effect of thalidomide is reduced, and the treatment effect of thalidomide on ulcerative colitis, especially left colon ulcerative colitis is improved.

The application relates to the technical field of pharmaceutical chemistry, in particular to a STAT3 inhibitor, a PROTAC molecule and a preparation method and application thereof. A novel STAT3 inhibitor is designed and synthesized as a ligand combined with a target protein, thalidomide is used as a ligand of an E3 ligase CRBN, a PROTAC molecule for targeted degradation of STAT3 protein is synthesized by connection of a connection chain Linker, the PROTAC molecule has a good degradation effect on STAT3 protein, and has good proliferation inhibition activity on various malignant tumor cells, for example, lung cancer cells, liver cancer cells and the like, and especially has a good industrial prospect in the application to the preparation of a drug for treating non-small cell lung cancer.

This invention relates to the field of biomedical technology, specifically disclosing an exosome for treating radiation-induced oral mucositis and its preparation method. The exosomes are prepared from human umbilical cord mesenchymal stem cells pretreated with FC-tagged IL-11, and thalidomide is encapsulated within the exosome lumen through incubation to form HUCMSCs. FI -exo-THD. This exosome exhibits excellent biocompatibility and targeting, significantly improving the delivery efficiency and therapeutic effect of thalidomide in the treatment of radiation-induced oral mucositis. Experimental results show that, compared with free thalidomide and other single-treatment exosomes, HUCMSCs... FI -exo-THD exhibits more significant effects in restoring cell viability and inhibiting apoptosis in X-ray-induced damage to human oral mucosal epithelial cells, increasing cell viability by more than 30% and reducing the apoptosis rate to below 10%. The preparation method of this invention is simple, reproducible, and suitable for large-scale production, providing a new strategy for the clinical treatment of radiation-induced oral mucositis.

This invention discloses an acidic tumor microenvironment-activated nanoprobe, its synthesis method, and its application, belonging to the field of nanomaterial preparation technology. Addressing the shortcomings of existing photosensitizers in photodynamic therapy (PDT), such as low treatment efficiency and lack of tumor targeting due to tumor microenvironment hypoxia, this invention utilizes metallic Fe... 2+ A low-pH-responsive smart nanoprobe was prepared by self-assembling the anti-angiogenic drug thalidomide and the FDA-approved photosensitizer hematoporphyrin monomethyl ether. Before degradation at the tumor site, the probe exhibits photodynamic therapy activity while its magnetic resonance imaging (MRI) signal is deactivated. As the material accumulates in the tumor tissue, under the low-pH stimulation of the tumor microenvironment, the MRI signal gradually activates, releasing thalidomide. This amplifies oxidative stress by increasing ROS / consuming GSH and inducing ferroptosis in tumor cells, ultimately resulting in a synergistic effect of chemokinetics / chemotherapy / photodynamic therapy on an excellent anti-tumor response.

The application discloses an enema preparation for treating ulcerative colitis, which contains 0.01-2g of thalidomide, 30-150ml of dimethyl sulfoxide, 1-5g of carbomer per liter of the enema preparation, and further comprises a pH regulator for adjusting the pH to 5.5-9.0 and deionized water. The enema preparation has simple components and preparation method and high biocompatibility, can improve the local concentration and residence time of thalidomide in the intestinal tract, reduce the side effects of thalidomide and improve the treatment effect of thalidomide on ulcerative colitis, especially left-sided ulcerative colitis.

The present invention belongs to the field of biopharmaceutical technology, and specifically relates to a polypeptide targeting IDO1 and an IDO1 protein degradation targeting chimera. The polypeptide targeting IDO1 provided by the present invention is a high-affinity and targeted IDO1 extracellular domain protein binding polypeptide successfully selected using phage display technology. The polypeptide has a strong binding force with the IDO1 extracellular domain structural protein, and has the characteristics of high sensitivity, high recognition efficiency and small molecular weight. The present invention further combines the above-mentioned polypeptide with the E3 ubiquitin ligase ligand thalidomide through rational design to obtain PROTAC, which has good cell entry ability and IDO1 targeted degradation ability, can make the therapeutic drug for cancer disease more selective, and provide higher therapeutic efficiency while reducing systemic toxicity. Therefore, the present invention can provide a new treatment strategy and effective technical support for the development of new tumor targeted drugs and the treatment of related cancers.

The invention discloses an application of thalidomide in preparation of a medicine for treating ischemic stroke, and a thalidomide drug-loaded nanogel as well as a preparation method and an application of the thalidomide drug-loaded nanogel. The drug-loaded nanogel comprises a polyacrylic acid skeleton, thalidomide loaded on the polyacrylic acid skeleton, and three functional polypeptides, namely transferrin, microglial cell targeting peptide and pH low-insertion peptide, which are coupled with the skeleton. Through the synergistic effect of the three polypeptides, the nanogel can penetrate through a blood brain barrier, accurately targets microglia cells in an ischemic area, and responsively releases thalidomide in an acidic microenvironment. In-vitro experiments show that the nanogel can effectively inhibit expression of inflammatory factors of microglial cells; in-vivo experiments show that the traditional Chinese medicine composition can significantly reduce the cerebral infarction volume, protect the blood-brain barrier, improve the neurological function and cognitive behavior of model animals and increase the survival rate. The invention provides a precise and efficient drug delivery platform for ischemic stroke treatment.

The invention relates to the technical field of medicinal chemistry, and particularly discloses 3, 5-diaryl-1, 2, 4-oxadiazole derivatives as well as a preparation method and application thereof. Based on the design principle of PROTAC molecules, a series of 3, 5-diaryl-1, 2, 4-oxadiazole derivatives are designed and synthesized by taking a derivative of a small-molecule inhibitor HP590 as an STAT3 protein ligand, taking an E3 ubiquitin ligase ligand thalidomide, and taking flexible alkyl chains with different lengths and relatively rigid cycloalkane as linkers. The compound has good STAT3 protein degradation activity, has a weak inhibition effect on normal cells while effectively inhibiting tumor cell proliferation, shows good selective inhibition activity, opens up a new direction for research and development of PROTAC compounds, enriches a compound structure type library, provides powerful support for subsequent drug design, and has good application prospects in the fields of tumor cell proliferation inhibition, tumor cell proliferation inhibition, tumor cell proliferation inhibition, tumor cell proliferation inhibition, tumor cell proliferation inhibition, tumor cell proliferation inhibition, tumor cell proliferation inhibition, tumor cell proliferation inhibition, tumor cell proliferation inhibition, tumor cell proliferation inhibition, tumor cell proliferation inhibition, tumor cell proliferation inhibition and tumor cell proliferation inhibition. The potential application prospect is wide.

The application provides application of thalidomide in preparation of antiviral drugs and belongs to the technical field of antiviral drugs. The application proves that thalidomide has inhibiting effect on viruses of various common infectious diseases of domestic pigs at the cellular level, especially has significant inhibiting effect on proliferation of African swine fever virus (ASFV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2) and porcine epidemic diarrhea virus (PEDV) in vitro. The application also discloses an antiviral composition composed of active ingredient thalidomide or pharmaceutically acceptable salts thereof and pharmaceutically acceptable carriers and / or excipients, and discloses application of the composition in preparation of viral infection inhibitors and / or in preparation of pharmaceutical preparations for preventing and / or treating viral infectious diseases, and provides a basis for development of broad-spectrum antiviral new drugs.