65 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.

The present invention discloses a BRD4 / PLK1 dual-target small molecule fluorescent probe and its preparation method and application, belonging to the field of biomedicine technology. The BRD4 / PLK1 dual-target small molecule fluorescent probe provided by the present invention has a structure shown in Formula I or a structure shown in Formula II. It has strong biological activity, high affinity with BRD4 / PLK1 family proteins, and high sensitivity. It can be used as a probe to identify BRD4 family proteins and for research on related physiological, pathological, and related diseases; it can be used for high-throughput screening of BRD4 / PLK1 dual-target inhibitors and their application in anti-tumor aspects; it can also be used for labeling BRD4 / PLK1 family proteins and tumor cells or tissues in which they are highly expressed. The probe of the present invention can be used as a probe to identify BRD4 / PLK1 dual-target proteins and BRD4 / PLK1 dual-target proteins have broad application prospects in physiological, pathological, and related diseases. In addition, the preparation method of the BRD4 / PLK1 dual-target small molecule fluorescent probe provided by the present invention has mild reaction conditions, cheap and readily available raw materials, and simple operation and post-processing.

Provided include methods, compositions and kits for treating ovarian cancer (e.g., platinum-resistant ovarian cancer) in a subject. The method can comprise administration of a combination of a PLK1 inhibitor and a DNA-damaging agent (e.g., carboplatin or gemcitabine) to the subject in a manner sufficient to inhibit progression of the 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 discloses a pharmaceutical composition for treating tumors and application thereof. According to the invention, the BrTAC with anti-tumor activity is constructed by adopting a specific branched skeleton and ligand molecules such as pomalidomide and BI 2536, and the degradation efficiency of target protein PLK1 can be greatly improved. Fluorescence imaging results prove that BrTAC can induce liquid-liquid phase separation in cells, and in-vivo experiment results show that compared with traditional bivalent PROTAC, BrTAC has a better effect in the aspect of PLK1 degradation.

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 invention provides novel compounds that induce selective polo-like kinase 1 (PLK1) degradation. Specifically, the present invention provides a bifunctional compound in which a PLK1 binding moiety and an E3 ubiquitin ligase-binding moiety are linked by a chemical linker. The present invention provides the compound, a method for preparing the same, and the use thereof. The compounds may be effectively utilized for preventing or treating PLK1 related diseases.

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.

Finding that vimentin is overexpressed in cancer cells and the PLK1-induced phosphorylation of vimentin leads to tumorigenesis and cancer metastasis, the present invention suggests two methods of reducing frequency of interaction between PLK1 and vimentin as a strategy for preventing tumorigenesis and cancer metastasis by reducing the migration and infiltration of cancer, and provides an application thereof.

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 provides stereoisomers, deuterated derivatives or stereoisomeric deuterated derivatives of a compound of Formula (I): wherein R1 and R2 are as described herein, or pharmaceutically acceptable salts, solvates thereof, which are useful as PLK1 inhibitors, pharmaceutical compositions comprising the same, and methods of preparing the same. And to the use thereof in the treatment of diseases and conditions caused by dysregulation of PLK1 activity and / or diseases and conditions associated with PLK1, such as cancer. # imgabs0 #

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.

Provided herein are methods of using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing hematological malignancies. The second active agent is one or more of an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, an EZH2 inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, a SUV420H1 / H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a BIRC5 inhibitor, or a chemotherapy.

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.

Provided include methods, compositions and kits for treating cancer (e.g., small cell lung cancer) in a subject. The method can comprise administrating a PLK1 inhibitor (e.g., onvansertib) or a combination of a PLK1 inhibitor and a chemotherapeutic agent (e.g., paclitaxel) 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 include methods, compositions and kits for treating cancer (e.g., small cell lung cancer) in a subject. The method can comprise administrating a PLK1 inhibitor (e.g., onvansertib) or a combination of a PLK1 inhibitor and a chemotherapeutic agent (e.g., paclitaxel) to the subject in a manner sufficient to inhibit progression of the cancer.

The invention discloses a novel PLK1 degradation agent based on a dihydropteridinone derivative or a pyrimidino diaza # imgabs0 # ketone derivative. The PLK1 degradation agent of the present invention is a proteolytic targeting chimera (PROTAC) that recruits the PLK1 protein into the CRBN E3 ubiquitin ligase via an optimized rigid linker. The compounds can induce PLK1 degradation and have improved drug properties, and can be used, for example, as a payload for antibody-drug conjugates (ADCs) 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.

The present invention relates to bifunctional compounds capable of inducing degradation of Polo- like kinase 1 (PLK1) via ubiquitin proteasome pathway. More specifically, the invention relates to bifunctional compounds and conjugates derived thereof, along with processes to prepare the compounds or conjugates, uses thereof and methods for treating diseases through modulation of Polo-like kinase 1 (PLK1). Specifically, the invention relates to the use of the bifunctional compounds or conjugates in the treatment of cancer.

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).

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.