39 results about "PLK1" patented technology

Provided include methods, compositions and kits for treating metastatic cancer in a subject. The method can comprise administering to a metastatic colorectal cancer patient an effective amount of a PLK1 inhibitor (for example, onvansertib) and an effective amount of bevacizumab, wherein the patient has not received any treatment comprising bevacizumab within at least three months prior to the administration of the PLK1 inhibitor and bevacizumab in a manner sufficient to reduce or inhibit progression of the metastatic cancer.

Provided include methods, compositions and kits for treating breast cancer in a subject. The method can comprise administrating to a subject a PLK1 inhibitor in combination with a chemotherapeutic agent or DNA damaging agent either in a standalone form or conjugated to an antibody targeting breast cancer cells to form an antibody drug conjugate in a manner sufficient to inhibit or reduce progression of the breast cancer. The breast cancer can be a HR+ breast cancer, or a breast cancer having negative, low or ultralow HER2 status. In some embodiments, the breast cancer is triple negative breast cancer with a negative, low or ultralow HER2 status.

Provided include methods, compositions and kits for treating metastatic cancer in a subject. The method can comprise administrating a treatment comprising inhibiting angiogenesis and a PLK1 inhibitor (for example, onvansertib) to the subject that has not received prior anti-angiogenic treatment, in a manner sufficient to reduce or inhibit progression of the metastatic cancer.

The invention belongs to the technical field of gene detection, and particularly relates to a brand new application of a DDX42 gene or an expression product thereof as an acute myelogenous leukemia (AML) diagnosis and prognosis biomarker. Specific high expression of DDX42 in bone marrow and peripheral blood samples of AML patients is revealed for the first time, the expression level of DDX42 is remarkably different from that of a healthy control group, and DDX42 can be detected through real-time fluorescent quantitative PCR, western blot and other methods and is used for diagnosis, differential diagnosis, disease state evaluation or risk stratification of AML. Meanwhile, the invention clarifies a molecular mechanism that DDX42 promotes AML cell proliferation and inhibits apoptosis and differentiation through PLK1 and LIMK1-CREB-DNMT1 signal axes, and verifies that a transcription factor ERG is an upstream forward regulatory factor for the first time. Based on the discovery, the invention not only provides a novel high-sensitivity molecular diagnosis marker for AML, but also lays a solid experimental foundation for developing a novel AML treatment strategy and a drug screening system targeting DDX42 and related signal channels thereof. The method has the advantages of mature detection method, high marker relevance, clear application prospect and the like.

Provided include methods, compositions and kits for treating metastatic cancer in a subject. The method can comprise administrating a treatment comprising inhibiting angiogenesis and a PLK1 inhibitor (for example, onvansertib) to the subject that has not received prior anti-angiogenic treatment, in a manner sufficient to reduce or inhibit progression of the metastatic cancer.

The present disclosure relates to a pyridinylpyrazole derivative or a pharmaceutically acceptable salt thereof and a composition for preventing or treating a protein kinase-related disease, which contains the derivative or salt as an active ingredient. Since the pyridinylpyrazole derivative of the present disclosure exhibits cytotoxicity by inhibiting polo-like kinase 1 (PLK1), which induces cell proliferation, when administered to an individual, it can be used for prevention or treatment of a protein kinase-related disease, specifically for prevention or treatment of cancer.

Provided include methods, compositions and kits for treating metastatic cancer in a subject. The method can comprise administrating a treatment comprising inhibiting angiogenesis and a PLK1 inhibitor (for example, onvansertib) to the subject that has not received prior anti-angiogenic treatment, in a manner sufficient to reduce or inhibit progression of the metastatic cancer.

The application provides application of a PLK1 inhibitor in preparation of a drug for treating ovarian hypercalcemia type small cell carcinoma. The drug containing the PLK1 inhibitor can effectively treat the ovarian hypercalcemia type small cell carcinoma, inhibit growth of a lesion of the ovarian hypercalcemia type small cell carcinoma, has a quick effect, and can produce obvious therapeutic effect 20 days after administration.

This invention discloses the application of glycyrrhizin, an effective extract of licorice, in the preparation of drugs for the prevention, improvement, or treatment of hepatocellular carcinoma. This invention is the first to discover that glycyrrhizin possesses significant anti-hepatocellular carcinoma activity, significantly inhibiting the proliferation of human liver cancer cells HepG2 and Huh7, and inducing cell morphological shrinkage, decreased adhesion, and cell death. Transcriptome sequencing and network pharmacology combined analysis showed that glycyrrhizin exerts its effects by regulating the PI3K-Akt signaling pathway and cell cycle pathway, and regulates 10 core targets, including CCNA2, PLK1, AURKA, AKT1, EGFR, CASP3, BIRC7, HK1, PAEP, and ALDH3A1. Molecular docking confirmed the stable binding of glycyrrhizin to these targets. TCGA clinical database validation showed that the expression levels of these core targets were significantly correlated with the prognosis of hepatocellular carcinoma patients. This invention clarifies for the first time the pharmacodynamics and molecular mechanism of glycyrrhizin against hepatocellular carcinoma, providing a safe, efficient, multi-target natural small molecule anti-liver cancer candidate drug with significant clinical translational and application value.

Disclosed herein include methods, compositions, and kits useful for use in the treatment of cancer in a subject. The methods may include administering a PLK1 inhibitor (e.g., onvansertib) to the subject to inhibit a hypoxia signaling pathway in the subject to reduce or inhibit the progression of the cancer.

This application discloses a SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) inhibitor and a Polo-like kinase I (PLK1) inhibitor for use in medicine, in particular for use in the treatment of cancer, more in particular of oesophageal cancer and colorectal cancer. Also disclosed is a kit of parts comprising a SHIP2 inhibitor and a PLK1 inhibitor for use in the treatment of cancer. Further disclosed are a kit of parts comprising a dosage form of a SHIP2 inhibitor and a dosage form of a PLK1 inhibitor and a pharmaceutical composition comprising a SHIP2 inhibitor and a PLK1 inhibitor.

Provided include methods, compositions and kits for treating cancer (e.g., RASWT colorectal cancer) in a subject. The method can comprise administrating an a PLK1 inhibitor (for example, onvansertib) or a combination of a PLK1 inhibitor and an EGFR inhibitor to the subject in a manner sufficient to inhibit progression of the cancer.

Novel dihydropteridone or pyrimidodiazepinone derivative based PLK1 degraders are disclosed. The present PLK1 degraders are proteolysis targeting chimeras (PROTACs) that recruit PLK1 protein into CRBN E3 ubiquitin ligase via optimized rigid linkers. The compounds may induce PLK1 degradation with improved drug properties and may be utilized for example, as a payload of antibody-drug conjugated (ADC) for the treatment of cancer.

Provided are a free base or pharmaceutically acceptable salt of a pyrazoloquinazoline compound of formula (I), which can be used as a PLK1 inhibitor, optionally in a crystalline form, and a solvate or hydrate thereof, wherein the pharmaceutically acceptable salt comprises a hydrochloride, sulfate, phosphate, maleate, fumarate, L-tartrate, citrate, L-aspartate, hippurate, L-glutamate, L-malate, adipate, glutarate, p-toluenesulfonate, and methanesulfonate of the pyrazoloquinazoline compound of formula (I), and also provided is a pharmaceutical composition comprising same, and a use thereof in the treatment of diseases and conditions caused by dysregulated activity of PLK1 and / or diseases and conditions related to PLK1, such as cancer.

Provided herein are methods of treating cancer using a combination of a compound provided herein (e.g., Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, or Compound 7, or a stereoisomer or mixture of stereoisomers, a pharmaceutically acceptable salt, a tautomer, a prodrug, a solvate, a hydrate, a co-crystal, a clathrate, or a polymorph thereof) and a second active agent. The second active agent is one or more of a PLK1 inhibitor, a BRD4 inhibitor, a BET inhibitor, a NEK2 inhibitor, a AURKB inhibitor, a MEK inhibitor, a PHF19 inhibitor, a BTK inhibitor, a mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BIRC5 inhibitor, or a DNA methyltransferase inhibitor.

Solutions to the problem of the invention are a method for selectively killing or removing a senescent cell, substance identification, and a method for purifying a senescent cell. Specifically, the invention includes an agent for removing a senescent cell, which is a drug for removing an in vivo senescent cell, the agent containing an inhibitor for glutaminase as an active ingredient, and a pharmaceutical composition containing the agent. The invention further includes a method for preparing a senescent cell, including the following steps (a) to (c): (a) synchronizing a cell with the G2 phase; (b) activating an intracellular p53 protein in the cell synchronized with the G2 phase; and (c) inhibiting polo-like kinase 1 (PLK1) activity in the cell treated in the step (b).

The present invention relates to a series of compounds for regulating activity of a protein kinase, in particular a compound for inhibiting activity of PLK1. The present invention further provides a pharmaceutical composition containing the compound, and a use of the compound and the pharmaceutical composition thereof in preparing a drug for preventing or treating diseases caused by and / or related to dysregulation of PLK1 kinase activity.

Disclosed herein include methods, compositions, and kits suitable for use in treating cancer. In some embodiments, the method comprises administrating a topoisomerase I inhibitor and onvansertib to a subject with cancer, thereby inhibiting progression of the cancer. The method can further comprise an angiogenesis inhibitor. The method can include sensitizing cancer cells to a topoisomerase I inhibitor, by contacting the cancer cells with a composition comprising onvansertib.

The invention provides a novel PLK1 inhibitor which can be used for preventing and / or treating diseases related to PLK1, such as tumors, has higher PLK1 inhibition activity and tumor cell killing activity, improves physicochemical properties such as solubility and permeability, and has higher bioavailability.

Provided include methods, compositions and kits for treating metastatic cancer in a subject. The method can comprise administering to a metastatic colorectal cancer patient an effective amount of a PLK1 inhibitor (for example, onvansertib) and an effective amount of bevacizumab, wherein the patient has not received any treatment comprising bevacizumab within at least three months prior to the administration of the PLK1 inhibitor and bevacizumab in a manner sufficient to reduce or inhibit progression of the metastatic cancer.

Provided include methods, compositions and kits for treating cancer in a subject. The method can comprise administrating an MTDP inhibitor (for example, paclitaxel) and a PLK1 inhibitor (for example, onvansertib) to the subject in a manner sufficient to inhibit or reduce progression of the cancer.

The application provides a construction of a targeted DNA nanocarrier and application of the targeted DNA nanocarrier in precise tumor gene therapy, and belongs to the technical field of nucleic acid nanomaterials. The construction of the targeted DNA nanocarrier is based on an assembling technology of 3D structural units which are stereoscopic growth in four directions and are raw materials of single nucleotides. The targeted DNA nanocarrier can efficiently load a gene therapy drug small interfering RNA (siRNA), specifically recognize tumor cells, and release the drug under the stimulation of high-concentration glutathione in cells, so as to inhibit the expression of PLK1 mRNA and protein and induce cancer cell apoptosis. The targeted DNA nanocarrier has the following characteristics: enhanced serum stability, specific targeting of cancer cells, and stimulative response release of the drug in the inside of the cancer cells, and is a tumor gene therapy method with application prospect.

The application relates to application of PLK1 protein in preparation of a product for identifying X sperm and Y sperm of mammals, enriching X sperm or determining the concentration of X sperm, and belongs to the technical field of biological detection. By detecting total proteins of X sperm and Y sperm of a cow, a marker protein PLK1 protein which is specifically expressed in X sperm but not in Y sperm is identified, and the PLK1 protein is further used for identification of X sperm and Y sperm, enrichment of X sperm and determination of the concentration of X sperm. Whether the PLK1 protein is expressed can be used to determine the type of sperm, X sperm can be enriched quickly and simply on the basis of not damaging the sperm, and the concentration of X sperm can be determined according to the expression amount of the PLK1 protein.

The invention provides a 2, 4-diarylaminopyrimidine derivative containing benzene and heteroaryl as well as a pharmaceutical composition and application thereof, and relates to the field of pharmaceutical chemistry. The invention relates to a 2, 4-diarylaminopyrimidine derivative containing benzene heteroaryl as shown in a general formula I, an optical isomer, a pharmaceutically acceptable salt, a solvate or a prodrug thereof, preparation methods of the derivative and the optical isomer, the pharmaceutically acceptable salt, the solvate or the prodrug thereof and a pharmaceutical composition taking the compound as an active ingredient, and substituent groups R1, R2, R3, R4, A, B and X have meanings given in the specification. The invention further relates to application of the compound shown in the general formula I and the pharmaceutically acceptable salt solvate or the prodrug of the compound in preparation of drugs for treating diseases caused by abnormal high expression of PLK1, EGFRL858R / T790M and EGFRL858R / T790M / C797S kinase, in particular to application in preparation of drugs for treating and / or preventing lung cancer. (I).

The present invention relates to inhibitors of polo-like kinase 1("PLK1"). In particular, the present invention relates to compounds that selectively inhibit the activity of PLK1, pharmaceutical compositions comprising a therapeutically effective amount of the compounds, and methods of use therefor, such as methods for treating PLK1-mediated diseases and disorders, such as cancer.

The invention provides a salt form and a crystal form of a PLK1 kinase inhibitor as well as a preparation method and application of the salt form and the crystal form. Specifically, the invention provides a salt form, a crystal form and a preparation method of a compound shown as a formula I, and application of the compound in preparation of drugs for treating diseases caused by disorder of PLK1 kinase activity and / or related diseases.

The application discloses an interfering RNA of PLK1 and application thereof, and belongs to the technical field of biological medicines. The application discloses application of a reagent for knocking down PLK1 in preparation of a medicine for preventing and treating pseudoallergy, wherein the reagent comprises siRNA for interfering with PLK1 gene expression, and the nucleotide sequence of the siRNA is shown as SEQ ID NO: 5-6. Through in-vitro cell experiments, it is proved that the expression level of the knocked-down PLK1 can improve morphological changes of RBL-2H3 cells in degranulation induced by C48 / 80, reduce cell apoptosis, and reduce HA and beta-HEX release amount, and has an obvious improvement effect on pseudoallergy; it is proved that PLK1 has a significant regulation effect on pseudoallergy, and provides a theoretical basis and experimental basis for exploring a potential mechanism and a treatment method of pseudoallergy.

The present invention relates to a use of TSG6 shRNA as a therapeutic agent for metastatic solid cancer. More specifically, the present invention can be usefully used for treating cancer in which metastasis occurs by PLK1, which is known to be overexpressed, particularly in cancer, and the active form thereof or TGF-beta / Smad signaling by reducing proliferation, migration, and invasiveness of metastatic cancer cells through gene therapy that suppresses TSG6 mRNA expression.