89 results about "PLK1" patented technology

A small-interference RNA (SiRNA) molecular directed to PLKI mRNA for killing tumor cells, its mixture and its application are disclosed. It is a double-stranded RNA molecular. Its nucleoside sequence is also disclosed.

The invention provides a kit for detecting 7 genetic markers of peripheral blood in early diagnosis of nasopharyngeal darcinoma. The kit comprises a peripheral blood total RNA extracting reagent, RT-PCR reaction liquid, time fluorescence quantitative RT-PCR reaction liquid and an SVM nasopharyngeal darcinoma diagnosis model, wherein the time fluorescence quantitative RT-PCR reaction liquid comprises primers of which the sequences are shown as SEQ IDNO:1-16; the primer sequences are SYBR Green fluorescence quantitative RT-PCR detection primers of the 7 genetic markers and reference gene GAPD; and the 7 genetic markers are HERC5, DLG7, PPARG, PLK1, KIF15, KLHL25 and MYST4. The invention also provides a using method for the kit. The kit has the advantages of high sensitivity, specificity and convenience, and can be used as aided diagnosis and early diagnosis technology for the nasopharyngeal darcinoma.

The invention discloses a novel dihydro pteridinone derivative, a preparing method thereof and application to medicine.The novel dihydro pteridinone derivative is characterized in that the structure general formula is shown in the formula (I) or (II) (see the formulas in the description).The dihydro pteridinone derivative can be used in a drug for treating cell proliferation diseases.The dihydro pteridinone derivative is simple in preparing method and greatly improves selectivity in Plk family while keeping good kinase inhibitory activity to Plk1 to improve selectivity to most kinds of kinase, targeting ability of the drug is improved, and toxic and side effects as well as untoward effects are reduced while the pharmacological effect is kept.

The present invention relates to a gene marker for diagnosis of human hepatocellular carcinoma (HCC), which is selected from the group consisting of IGF2, VEGF, MET, SUMO2, CDK4, MMP9, PLK1, AFP, Rb1, CYP3A4, LAP3, RIZ, DLC1, ITIH1, FetB, ALDOB, SULT2A1, ASS, HP, SERIND1, EI24, HGD, RODH, F2, SORD, and KNG. The HCC is diagnosed effectively and efficiently based on detecting the expression levels of the present gene marker from the liver tissue sample of an individual to be diagnosed.

The invention relates to the field of the pharmaceutical chemistry, in particular to aromatic dihydrazide compounds, a preparation method of the compounds, pharmaceutical composites with the compounds and medical applications of the compounds, especially the applications of the compounds used as Polo like kinase 1 inhibitor.

The invention relates to the application of a compound T521 or analogues thereof in the preparation of an antitumor drug, the application is on the basis of combining the compound T521 or the analogue of the compound T521 with Plk1 (Polo-like kinases1) PBD (Polo Box Domain), so that the function that the Plk1 is combined with a nature-ligand thereof is inhibited. The invention also relates to a screening method of a Plk1 inhibitor taking a key amino acid space structure as a target in a Plk1 PBD active center.

The invention relates to aminopyrimidine compounds useful for treating diseases mediated by polo-like kinase 1 (Plk1). The invention also relates to the therapeutic use of such aminopyrimidine compounds and compositions thereof in treating disease states associated with abnormal cell growth and unwanted cell proliferation.

The present invention relates to a compound represented by Formula [I] or a pharmaceutically acceptable salt or ester thereof: wherein: X1, X2, X3, and X4, which may be identical or different, are each C or N, provided that none to two of X1, X2, X3, and X4 is / are N; Y is CH or N; R1, R1′, R2, R2′, R3, R3′, R4, and R4′, which may be identical or different, are each a hydrogen atom, a lower alkyl group, or the like; R5 is a hydrogen atom or a methyl group; R6 and R7, which may be identical or different, are each a hydrogen atom, a lower alkyl group, or the like; R8 and R8′, which may be identical or different, are each a hydrogen atom, a lower alkyl group, or the like; R9 is an aryl group or a heteroaryl group which may be substituted; and n is an integer from 1 to 3, and a PLK1 inhibitor or an anticancer agent containing the same.

The present invention provides pyrimidinediamine compounds useful for inhibiting kinase activity, including the activity of polo-like kinase 1 (PLK1). Also provided are pharmaceutical compositions comprising these compounds and methods of treating diseases associated with kinase activity, in particular enhanced PLK1 catalytic activity, such as diseases associated with abnormal cell proliferation, including neoplastic disorders.

The invention provides an amion thiazolidone compound, as shown in a formula I, wherein A1 is aryl or ceteroary; A2 is benzene ring or substituted benzene ring, double benzene nucleus or substituted double benzene nucleus, pyridine ring (including 2-, 3-, 4-pyridine) or substituted pyridine ring; and R1, R2, R3, R4, R5 and R6 are respectively H, halogen, hydroxy, cyan, amino or nitro or C1-C6 alkyl or C1-C6 alkoxy and the like; and R7 and R8 are respectively H, C1-C6 alkyl or C3-C6 naphthene base. The compound in the formula I comprises hydrate of the compound, solvate, stereoisomer, N-oxide, salt and crystalline forms which exist in various forms. Bioactivity tests show that: the compound in the formula I can restrain the activities of polo-like kinase 1 (PLK1) inside and outside the human body, and can be used for preparing antitumor drugs. The invention further provides a method for preparing the compound in the formula I.

MiniVectors and compositions containing MiniVectors that target ovarian cancer genes selected from FOXM1, AKT, CENPA, PLK1, CDC20, BIRC5, AURKB, CCNB1, CDKN3, BCAM-AKT2, CDKN2D-WDFY2, SLC25A6, CIP2A, CD133, ALDH1A1, CD44, SALL4, and / or PRDM16, alone or in any combination, are provided, along with uses in the treatment of ovarian cancer.

The invention provides a targeted siRNA delivery bionic nanoparticle which is a PBAE / siRNA composite nanoparticle wrapped by a cancer cell membrane, and further provides a preparation method and application thereof. According to the method, bionic nanoparticles are adopted, silencing of the Plk1 gene is efficiently achieved, apoptosis of cancer cells is induced, and proliferation of the cancer cells is inhibited. According to the method disclosed by the invention, a system capable of realizing efficient siRNA delivery is constructed. The polypeptide can specifically recognize homotype cancer cells, accumulate in the cancer cells, successfully escape from lysosome after entering the cells, efficiently silence target genes and inhibit expression of the target genes to cause cancer cell apoptosis, thereby inhibiting tumor growth.

The invention relates to the field of medicinal chemistry, and in particular relates to 2-phenylaminopurine compounds, a preparation method for the compounds, a medicinal composition containing the compounds, and medical applications for the compounds, and in particular an application for the compounds as Polo-like kinase 1 inhibitors.

Belonging to the field of tumor gene therapy, the present invention provides an anti-tumor RNA interference plasmid-lipidosome-heparin complex targeting the human FAK and FLK1 genes. The RNA interference expression vector can express a RNA interference sequence aimed at a target site shown by SEQ ID NO:1 on the FAK gene and a RNA interference sequence aimed at a target site shown by SEQ ID NO:2 on the FLK1 gene in the body. The FAK and PLK1 dual-gene RNA interference plasmid prepared by the present invention can effectively inhibit the growth of lung cancer cells and induce the lung cancer cells to be apoptosed. A tumor inhibition experiment conducted in the body also indicates that the FAK and PLK1 dual-gene RNA interference plasmid-lipidosome-heparin complex can notably inhibit the growth of manifold tumors and prolong the lifetime of tumor-bearing mice. The product of the anti-tumor RNA interference plasmid-lipidosome-heparin complex has obvious efficacy and can reduce dosage and improve the life quality of patients, thus having a good application prospect.

A genetic biomarker panel is provided for prognosing late onset ER+ breast cancer relapse, in a breast cancer survivor patient. Kits are also provided for measuring levels or the presence of an identified panel of genetic biomarkers. Methods are also provided for identifying a breast cancer survivor patient at a relatively high risk of suffering a breast cancer relapse within 8 years of diagnosis, and therefore suitable for treatment with an aggressive chemotherapeutic regimen. The method may also be used for identifying a breast cancer survivor patient not at high risk of suffering a breast cancer relapse within 8 years of diagnosis, and thus not suitable for treatment with an aggressive chemotherapeutic regimen. The genetic biomarker panel includes an oligonucleotide / nucleic acid sequence specific for the following genes: MKI67, SPAG5, ESPL1, PLK1, or a genetic panel for MKI67, SPAG5, ESPL1, PLK1 and PGR.

Found in various eukaryotic organisms, polo-like kinases (collectively, Plks) are a conserved subfamily of Ser / Thr protein kinases that play critical roles in cell proliferation. Provided herein are compounds that specifically inhibit the activity of Plks, specifically Plk1. Further provided herein are methods for use of the compounds for the treatment of hyperproliferative disorders, particularly cancer. Also provided are uses of the compounds for the preparation of a medicament.

The invention relates to an anti-tumor engineering exosome, a preparation method and application. The anti-tumor engineering exosome comprises an exosome body, wherein an anti-tumor nucleic acid medicine and a photosensitizer are coated in the exosome body. Compared with a natural exosome Nex, the engineering exosome Nex @ siRNA / Ce6 has the following characteristics that 1, tumor cells are killed in a targeted way, and no killing effect is achieved on normal cells; 2, the tumor cell apoptosis is promoted through silencing PLK1 genes; the mouse immune system is activated through inhibiting the PD-L1 expression; and 3, the photosensitizer Ce6 in the engineering exosome generates active oxygen under the illumination; the targeted killing of the tumor cells is promoted through the photodynamic effect generated under the illumination; the active oxygen has the effect of damaging the endosome membrane; the siRNA is promoted to escape into the cytoplasm from the endosome; the gene inhibition effect of the cancer cells is improved; the active oxygen can also promote the M2 type macrophage to turn to the M1 type macrophage; and the anti-tumor effect is synergistically enhanced.

The present invention discloses a fusion protein for treating a breast cancer, wherein the fusion protein is Her2 single-chain fragment antibody-polypeptide, the Her2 single-chain fragment antibody is capable of targeting a Her2 receptor locating on a surface of a breast cancer cell, and the polypeptide is capable of carrying siRNA. The polypeptide includes a protamine polypeptide. The siRNA includes PLK1-siRNA, which is capable of restraining an expression of a knubble malignant phenotype gene. The fusion protein for treating the breast cancer is capable of carrying the PLK1-siRNA, and targeting and importing a Her2 positive breast cancer cell specifically, so as to bring the medicament into the cell. The treatment of the breast cancer is capable of generating a strong effect for restraining the breast cancer growth and transfer, may break a gene suppression effect of the existing antisense oligonucleotide and ribozyme, and becames a novel anti-Her2 gene medicament for treating the breast cancer.

The invention relates to the field of medicinal chemistry, and particularly relates to 2-amino-quinazolines compounds, preparation methods of the 2-amino-quinazolines compounds, medicinal compositions containing the compounds, and medical applications of the 2-amino-quinazolines compounds and the medicinal compositions, especially applications of the 2-amino-quinazolines compounds and the medicinal compositions serving as Polo-like kinase1 inhibitors.

The invention relates to the field of medicinal chemistry, and particularly relates to pyridino-miazines compounds, preparation methods of the pyridino-miazines compounds, medicinal compositions containing the compounds, and medicinal applications of the pyridino-miazines compounds and the medicinal compositions, especially applications of the pyridino-miazines compounds and the medicinal compositions serving as Polo-like kinase 1 inhibitors.

Isolated peptide substrates of Plk1 and nucleic acids encoding these peptides are disclosed. The peptides include two to ten repeats of the amino acid sequence set forth as X1X2AX3X4X5PLHSTX6X7X8X9X10X11X12 (SEQ ID NO: 1), in which within each repeat X1, X2, X6, X7, X8, X9, X10, X11, and X12 are each independently any amino acid or no amino acid, and X3 and X4 are each independently any amino acid. Methods of using these peptides to detect Plk1 activity in a sample are also disclosed. In some examples, the method includes contacting a sample with a disclosed peptide substrate of Plk1 in the presence of adenosine triphosphate, or an analog thereof, for a period of time sufficient for Plk1 to phosphorylate the PBIPtide. The presence and / or amount of the phosphorylated and / or the unphosphorylated peptide is detected, thereby detecting and / or quantitating Plk1 kinase activity in the sample.

The invention relates to aminopyrimidine compounds useful for treating diseases mediated by polo-like kinase 1 (Plk1). The invention also relates to the therapeutic use of such aminopyrimidine compounds and compositions thereof in treating disease states associated with abnormal cell growth and unwanted cell proliferation.

The present invention provides compounds of Formulae (I)-(V), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. In one aspect, compounds of the present invention are useful as glycosyltransferase inhibitors, in particular, O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) inhibitors. In another aspect, compounds of the present invention are useful as kinase inhibitors, in particular, PLK1 inhibitors, GSK3P inhibitors, or MAPKAPK2 inhibitors. The present invention further provides methods of using the inventive compounds, e.g., as biological probes to study the inhibition of OGT and / or kinase activity and as therapeutics, e.g., for the treatment of OGT-associated and / or kinase-associated conditions.

The invention provides a PLK1 inhibitor, and a preparation method and an application thereof. The PLK1 inhibitor is a compound represented by general formula (I) shown in the description, and stereoisomers or pharmaceutically acceptable salts thereof. All groups in the formula (I) are defined as in the description. The PLK1 inhibitor can specifically bind to a DNA sequence in a PLK1 gene transcription promoter region, represented by SEQ: NO:1, in a high strength manner, inhibits transcription of the PLK1 gene, inhibits the expression of a PLK1 protein, causes tumor cell growth inhibition or apoptosis, can traverse through a cell membrane and a nuclear membrane and resist nuclease hydrolysis, and also solves the drug resistance problem of micro-molecular kinases inhibitors.

The invention relates to a pyrazolo[3, 4-d]pyrimidin-3-one derivative as shown in a formula (I) and / or pharmaceutically acceptable salt thereof, a composition containing the compound as shown in the formula (I) and / or pharmaceutically acceptable salt thereof, a preparation method of the derivative, and an application of the derivative as Wee1 and / or PLK1 inhibitors and as sensitizers for chemotherapy or radiotherapy of cancer. The pyrazolo[3, 4-d]pyrimidin-3-one derivative disclosed by the invention can effectively inhibit Wee1 and / or PLK1 and related signal channels, and has a good effect of treating and / or relieving cancers.

The invention relates to modulating Cdc14B levels (cell division cycle 14 homolog B) and / or Cdh1 (Fzr1 protein, CDC20-like 1b, or fizzy-related protein) levels to sensitize cells to DNA damage by increasing the abundance of Plk1 (polo-like kinase 1) in a target cell. In certain embodiments, the invention relates to modulating Plk1 levels, and in particular to increasing Plk1 levels, to sensitize target cells such as cancer cells to cell death or apoptosis. In certain embodiments, the invention relates to inhibitors of Cdc14B and Cdh1 that sensitize tumor cells to chemotherapy or radiation induced cell death or apoptosis. In addition to applications relating to cancer therapies and diagnostics, the Plk1 modulators and assays will be employed for identifying novel drugs or drug candidates useful for various proliferative and / or differentiative disorders such as major opportunistic infections, immune disorders, cardiovascular diseases and inflammatory disorders.

The invention relates to the field of medicinal chemistry, and in particular relates to 2-imidazole ring-substituted thiophene PLK1 (Polo-like kinase 1) inhibitors, a preparation method for the inhibitors, a medicinal composition containing the compounds, and medical applications for the compounds, and in particular an application for the compounds as Polo-like kinase 1 (PLK1) inhibitors.

The present invention relates to 4-pyrimidinylamino-benzenesulfonamide derivatives of general formula (I) and pharmaceutically acceptable salts, solvates, hydrates, regioisomeric and polymorphic forms thereof, processes for manufacturing of them, the use of them, as well as pharmaceutical compositions containing at least one of them as pharmaceutically active agent(s) together with pharmaceutically acceptable carrier, excipient and / or diluents, especially for the inhibition of polo-like kinases (PLKs) and the treatment of cancer. Said 4-pyrimidinylamino-benzenesulfonamide compounds have been also identified as new drug candidates for the prevention and / or treatment of infectious diseases like bacterial diseases e.g. tuberculosis, including the currently multidrug-resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) as well as for preventing tuberculosis.

The present inventions relate to methods and compositions useful for improving the efficiency of inducing the generation of neurons from non-neuronal cell types, for example, by contacting the cell or cell culture medium with one or more agents which inhibit Activin and / or PLK1 signaling. Also disclosed are methods for promoting neuron survival, for example, by inhibiting Activin and / or PLK1 signaling, and methods for promoting the survival of intermediates in a cell differentiation pathway, for example, by inhibiting Activin and / or PLK1 signaling.