120 results about "ABL" patented technology

Compounds of the present invention, alone and in combination with other active agents, find utility in the treatment of hyperproliferative diseases, mammalian cancers and especially human cancers including but not limited to for example malignant melanomas, myeloproliferative diseases, chronic myelogenous leukemia, acute lymphocytic leukemia, a disease caused by c-ABL kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof.

The invention discloses a preparation method of a magnetic sandwich nano immunosensor and application of the preparation method. The preparation method is characterized by comprising the following steps: mixing and stirring a collaurum solution and silane ferriferrous oxide into a colorless and transparent solution, and carrying out magnetic separation by externally applying a magnet to obtain FE3O4/Au colloid nano magnetic beads; loading horse radish peroxidase (HRP) and secondary antibodies of an object to be measured to the FE3O4/Au colloid nano magnetic beads to obtain a secondary antibody probe Fe3O4/Au-HRP-Ab2; electrically depositing Au to a glassy carbon electrode, loading primary antibodies of the object to be measured, and then closing non-specific active sites by using protein to obtain an Abl/Au/GCE electrode; and finally, loading antigen to the Abl/Au/GCE electrode, and then obtaining the sandwich nano immunosensor by combining the magnet probe. The magnetic sandwich nano immunosensor can be used for measuring the concentration of melamine, tonyred, clenbuterol or estrogen in food and has the advantages of high detection speed, high accuracy and sensitivity and low cost.

Compounds represented by Formula (I):

or stereoisomers or pharmaceutically acceptable salts thereof, are inhibitors of least two of the Abl, Aurora-A, Blk, c-Raf, cSRC, Src, PRK2, FGFR3, Flt3, Lck, Mek1, PDK-1, GSK3β, EGFR, p70S6K, BMX, SGK, CaMKII, Tie-2, IGF-1R, Ron, Ret, and KDR kinases in animals, including humans, for the treatment and/or prevention of various diseases and conditions such as cancer.

The use of a compound for the manufacture of a medicament for the prophylaxis or treatment of: A. a disease state or condition mediated by a kinase which is BCR-abl, VEGFR, PDGFR, EGFR, Flt3, JAK (e.g. JAK2 or JAK3), C-abl, PDK1, Chk (e.g. Cbk1 or Chk2), FGFR (e.g. FGFR3), Ret, Eph (e.g. EphB2 or EphB4), or Src (e.g. cSrc); or B. a cancer in which the cancer cells thereof contain a drug resistant kinase mutation which is: (a) a threonine gatekeeper mutation; or (b) a drug-resistant gatekeeper mutation; or (c) an imatinib resistant mutation; or (d) a nilotinib resistant mutation; or (e) a dasatinib resistant mutation; or (f) a T670I mutation in KIT; or (g) a T674I mutation in PDGFR; or (h) T790M mutation in EGFR; or (i) a T315I mutation in abl; or C. a cancer which expresses a mutated molecular target which is a mutated form of BCRabl, c-kit, PDGF, EGF receptor or ErbB2; or D. a disease mediated by a kinase containing a mutation in a region of the protein that binds to or interacts with other cancer agents but does not bind to or interact with the compounds of formula (I) or (I′), for example a mutated kinase selected from c-abl, c-kit, PDGFR including PDGFR-beta and PDGFR-alpha, and ErbB family members such as EGFR (ErbB1), HER2 (ErbB2), ErbB3, and ErbB4, members of the Ephrin receptor family including EphA1, EphA2, EphA3, EphA4, EphA5, EphA8, EphA10, EphB1, EphB2, EphB3, EphB5, EphB6, c-Src and kinases of the JAK family such as TYK2; wherein the compound is a compound of the formula (I or I′): or a salt, solvate, tautomer or N-oxide thereof wherein R^0′, R¹, R^1′, R^2′, R^3′, R^4′, A′, X′, E, A and M are as defined in the claims.

Compounds represented by Formula (I):

or stereoisomers or pharmaceutically acceptable salts thereof, are inhibitors of least one of the Abl, Aurora-A, Blk, c-Raf, cSRC, Src, PRK2, FGFR3, Flt3, Lck, Mek1, PDK-1, GSK3β, EGFR, p70S6K, BMX, SGK, CaMKII, Tie-2, IGF-1R, Ron, Met, and KDR kinases in animals, including humans, for the treatment and/or prevention of various diseases and conditions such as cancer.

The invention belongs to the field of gene detection, and in particular relates to a multiplex PCR (polymerase chain reaction) kit for detecting leukemia fusion genes. The kit comprises a conventional multiplex PCR component, and chimeric primer and common primer pairs aiming at the common leukemia fusion genes. Chimeric primers are sequences of adding common primers to the 5' ends of specific primers of seven shear isomers of the common leukemia fusion genes BCR/ABL, PML/RARalpha, AML1/ETO and E2A/PBX1. By using the multiplex PCR kit for detecting the leukemia fusion genes, seven leukemia fusion genes including AML1/ETO, BCR/ABLe1a2, BCR/ABLe13a2, BCR/ABLe14a2, PML/RARalphaL, PML/RARalphaS and E2A/PBX11 with high incidence can be simultaneously detected, so that the consumption of reagents can be saved, the detection cost can be reduced, and meanwhile, the detection efficiency is improved. Moreover, the highest detection sensitivity of the kit can reach 10 copies per 25mu L, and the kit is simple in operation and high in clinical detection rate, so that the kit has clinical popularization and application values.

The invention discloses primers, probes and a kit for detecting leukemia-related fusion genes. The primers and probes are designed according to specificity of eight types of fusion genes such as BCR/ABL, PML/RAR alpha, AML1/ETO and TEL/AML1. The primers, probes and kit have high sensitivity and good specificity. The primers, probes and kit can detect 10 copies of a mutational sample. The kit utilizes a one-step real-time fluorescent quantitative reverse transcription polymerase chain reaction method to detect a sample to be detected, realizes reverse transcription and quantitative PCR in a reaction system, only needs one-step fluorescent PCR amplification, is free of a reagent and pipe cover opening in the reaction process, has detection time of 90min and is operated simply. The kit has the advantages of high sensitivity, good specificity, low price, fastness and simple operation and has a high scientific research value and a high clinical application value.

The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated tyrosine kinase activity, particularly diseases associated with the activity of PDGF-R, c-Kit and Bcr-abl.

The invention provides a method and kit for quantitative detection of BCR-ABL fusion genes. The specific technical scheme comprises that two BCR-ABL fusion genetypes are detected only by two differentupstream primers, a common downstream primer, a fluorescent labeled probe and a set of ABL internal reference gene detection system. With use of the specific primers and probes provided by the invention, the two fusion types of BCR-ABL can be detected only by one tube of a material, and the kit has the advantages of high specificity, good sensitivity and high accuracy.

The invention discloses cryptotanshinone pharmaceutical composition and an application thereof in preparation of a CML (chronic myeloid leukemia) treatment drug. The cryptotanshinone pharmaceutical composition contains cryptotanshinone and a tyrosine kinase inhibitor, with the adoption of cryptotanshinone for treatment, protein expression level of Bcr-Abl genes in CML K562 and multi-drug resistantstrains K562/ADM cells can be remarkably reduced, cell proliferation inhibition ratio of the tyrosine kinase inhibitor is increased, and apoptosis rate of CML K562 cells and K562/ADM cells can be remarkably increased through combination of cryptotanshinone and the tyrosine kinase inhibitor. With the adoption of the cryptotanshinone pharmaceutical composition, chemosensitivity of tyrosine kinase can be improved, chemotherapy drug dosage of a patient is reduced, toxic and side effects on a human body are reduced, and a new treatment scheme is provided for clinical treatment of CML.

This invention relates to a pharmaceutical composition useful for treating chronic myeloid leukemia where Bcr-Abl kinase is constitutively expressed in animals and humans, and a treatment of chronic myeloid leukemia (CML) by a composition comprising an effective amount of analogs and/or salts of chlorogenic acid. The analogs are preferably sodium chlorogenate (Na-Chl) or potassium or ammonium salts, which were prepared from Chlorogenic acid or its analogs.

The invention provides a method, a kit and an oligonucleotide for detecting relative expression of the MLL5 gene in a sample, and all relate to an upstream primer MLL5-F for detection, an upstream primer MLL5-R for detection and a probe MLL5-Probe for detection, and an upstream primer ABL-F for the internal reference gene ABL, a downstream primer ABL-R and a probe ABL-Probe. The relative expression of the MLL5 gene in clinical samples can be rapidly detected. The invention can be applied to evaluation of therapeutic effect and prediction of prognosis.

The present invention relates to novel compounds selected from substituted oxazole derivatives that selectively modulate, regulate, and/or inhibit signal transduction mediated by certain native and/or mutant tyrosine kinases implicated in a variety of human and animal diseases such as cell proliferative, metabolic, allergic, and degenerative disorders. More particularly, these compounds are potent and selective c-kit, bcr-abl and Flt-3 inhibitors.

The invention provides a mouse model of acute lymphoblastic leukemia and a modeling method, and relates to the field of biotechnology. The preparation method comprises the following steps: infecting IL-7 stimulated hematopoietic cells with retroviruses with BCR-ABLP190; and transfusing the stimulated hematopoietic cells to syngenic mice. The method has the advantages of being simple and easy to implement in a modeling process and capable of establishing the ph+ALL mouse model in one step. According to the mouse model of the acute lymphoblastic leukemia provided by the invention, the sorted BCR-ABL+B cells are transfused to the syngenic mice for the second time without irradiation treatment, with performance consistent with that of mice of first episode; the model is good in stability; and in addition, the uniformity of recipient mice is enhanced and such risks as accidental death of the recipient mice due to irradiation are reduced.

The present invention relates to novel proteins that inhibit the activity of tyrosine kinases. In particular, the invention provides a tyrosine kinase inhibitor protein consisting of the cap region of a c-Abl protein. The invention also relates to the use of tyrosine kinase inhibitor proteins in the treatment and diagnosis of diseases, in particular cancers, in humans.

The invention discloses an assay kit for testing the relative expression of core-binding factor (CBF) beta/myosin 11 fusion genes, and the kit comprises red blood cell lysis buffer, TRIzol, chloroform, absolute ethyl alcohol, ReverTraAceqPCRRTKit, testing system polymerase chain reaction (PCR) reaction solution, positive control substance and negative control substance, and is characterized in that the testing system PCR reaction solution comprises THUNDERBIRDqPCRMIX, primers of CBF beta/MYH11-F, CBF beta/MYH11-A-R, CBF beta/MYH11-D-R and CBF beta/MYH11-E-R for amplifying a target gene, probe of CBF beta/MYH11-Prob, primers of abl-F and abl-R for amplifying an internal control gene, and probe of abl-Probe. The assay kit can be used for testing the expression level of the CBF beta/myosin 11 fusion genes of a patient suffering from human acute myelognous leukemia (AML), so the test time can be effectively saved, and the test precision is improved.

The invention relates to a mixed gene for a detecting fusion gene. A gene sequence of the mixed gene is shown in SEQ ID NO:1. The mixed gene comprises a BCR-ABL fusion gene shown in SEQ ID NO:2, an AML-ETO fusion gene shown in SEQ ID NO:3, a PML-RARA fusion gene shown in SEQ ID NO:4 and an ABL reference gene shown in SEQ ID NO: 5. The invention further relates to standard plasmid containing the mixed gene, and the standard plasmid comprises PUC57 plasmid shown in SEQ ID NO: 6. The invention further relates to a kit containing the standard plasmid and further relates to a preparation method ofthe standard plasmid. The mixed gene has the advantages that the mixed gene can be applied to establishing a double-standard curve which is used for quantitatively detecting BCR-ABL, RUNX1-RUNX1T1 (AML-ETO) and PML-RARA fusion gene in a leukemia related fusion gene in human marrow or a peripheral blood sample; detection efficiency and accuracy are effectively improved, manual operation errors arereduced, and multi-plasmid pollution is prevented from happening; the lowest detection copy number of the standard plasmid is 1*10<0> per ml; operation is simple, pollution is not prone to happening,the detection range is large, and detection cost can be effectively reduced.

The present invention relates to the field of chemical medicines, in particular to compounds as represented by formula I having BCR-ABL kinase inhibitory activity, or pharmaceutically acceptable salt, isomer, solvate, crystal or prodrug thereof, and pharmaceutical composition containing the compounds, and application of the compounds or compositions in drug preparation. The compounds of the present invention have strong inhibitory effect on BCR-ABL kinase, and can be used to treat diseases such as tumors.

The invention belongs to the technical field of image analysis, and discloses a DNA fluorescence in situ hybridization BCR/ABL fusion state detection method and a detection system, which are characterized in that a CNN identification model is utilized to generate pseudonucleus staining of cells from a phase difference image, and FISH cell nucleuses are positioned and classified; and positioning and classifying each independent fluorescence signal, and dividing the number of color development points of the same classification in each photo by the total number of display points in the photo to obtain a BCR/ABL fusion ratio. The invention provides a system for detecting the fusion level of cell nucleuses and BCR/ABL genes by analyzing fluorescence in situ hybridization (FISH) images and calculating the image ratio of the number of abnormal cell nucleuses related to all classified cell nucleuses as an index for classifying the BCR/ABL gene fusion states of corresponding tumor samples. The detection method is high in detection efficiency, accurate in detection result and capable of achieving automatic detection.