46 results about "ABL Tyrosine Kinase" patented technology

The invention described herein relates to novel genes and their encoded proteins, termed Mutants Associated with Resistance to STI-571 (e.g., T315I Bcr-Abl), and to diagnostic and therapeutic methods and compositions useful in the management of various cancers that express MARS. The invention further provides methods for identifying molecules that bind to and / or modulate the functional activity of MARS.

The present invention relates to a method of treating chronic myelogenous leukemia in a subject comprising administering to the subject a compound, such as N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide, that inhibits the T315I mutation in BCR-ABL tyrosine kinase, or a pharmaceutically acceptable salt thereof. The present invention also relates to a pharmaceutical composition comprising a compound such as N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide, that inhibits the T315I mutation in BCR-ABL tyrosine kinase, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

The invention provides a protein degradation targeting BCR-ABL compound as shown in a formula (I) and an application thereof to resisting tumors. The compound as shown in the formula (I) has the effects of degrading and restraining BCR-ABL targeting protein, and mainly consists of four parts of a first part: BCR-ABL-TKIs which is a compound having BCR-ABL tyrosine kinase restraining activity, a second part: LIN which is a link unit, a third part: ULM which is a VHL or CRBN protease micromolecule ligand having a ubiquitination function, and a fourth part: a group A which is carbonyl and is used for performing covalent bonding on the BCR-ABL-TKIs and the LIN and covalent bonding on the LIN and the ULM. A series of compounds designed and synthesized by the invention have broad pharmacological activity, have the functions of degrading BCR-ABL protein and restraining BCR-ABL activity, and can be used for pertinent tumor treatment. (As shown in the description)

Truncation variants of BCR-ABL mRNA that produces BCR-ABL proteins with a truncated C-terminus and its role in resistance to treatment with kinase inhibitors is described. Vectors for expressing the truncated gene products are described as well as recombinant cells that express the truncated gene products from cDNA constructs. Also provided are methods compositions and kits for detecting the BCR-ABL truncation variants. Also provided are methods for determining the prognosis of a patient diagnosed as having myeloproliferative disease, and methods for predicting the likelihood for resistance to a treatment with tyrosine kinase inhibitor in a patient diagnosed as having myeloproliferative disease. Additionally, methods for screening BCR-ABL tyrosine kinase domain inhibitors which rely on the recombinant cells are also disclosed.

Methods of diagnosing a tauopathy and predicting whether a subject will develop a tauopathy are provided. Also provided are antibody preparations that specifically bind to tau phosphorylated at tyr394 and / or tyr310. Methods of inhibiting tau phosphorylation in a cell and methods of treating a subject having a tauopathy are additionally provided. Methods of treating a subject at risk for a tauopathy are also provided. Additionally, non-human mammals comprising a transgene encoding an abl tyrosine kinase are provided. Also provided are methods of evaluating whether a compound inhibits development of a tauopathy.

In the field of pharmaceutical chemistry compounds of general formula I having heteroaryl alkynyl moiety or pharmaceutically acceptable salts, isomers, solvates, crystals or prodrugs thereof, and pharmaceutical compositions including these compounds, as well as uses of these compounds and compositions thereof in the manufacture of a medicament. The compounds have a strong inhibitory effect on BCR-ABL tyrosine kinase and are useful for treating diseases, such as tumors.

An oral pharmaceutical formulation containing an effective amount of NRC-AN-019 including its pharmaceutically acceptable salts and polymorphs such as Form I, Form II and Form III thereof to improve the bioavailability intended for self-emulsification upon its contact with the gastro-intestinal fluid. The invention also relates to a process for the preparation of oral solution containing NRC-AN-019 in an effective concentration for the better therapy against Chronic Myeloid Leukemia as BCR-ABL tyrosine kinase inhibitor and against other tumors such as head and neck cancer, prostate cancer and the like.

The invention discloses application of a substance for inhibiting phosphorylation of a 357 tyrosine residue of a YAP protein to prevention of atherosclerosis. The substance for inhibiting phosphorylation of the 357 tyrosine residue of the YAP protein is an Src / c-Abl tyrosine kinase double inhibitor or a c-Abl inhibitor or an Src inhibitor; bosutinib is adopted as the Src / c-Abl tyrosine kinase double inhibitor; and experiments prove that the bosutinib prevents atherosclerosis, treats atherosclerosis, decreases the area of plaques of atherosclerosis, reduces lipid deposition, decreases the collagen content, inhibits forming of the plaques of atherosclerosis, inhibits activation of vascular endothelial cells and inhibits the expression level of adherence factors by inhibiting phosphorylation of the 357 tyrosine residue of the YAP protein. The substance has significant application value.

The present disclosure provides a compound of formula (I) targeting and degrading BCR-ABL protein and its use in the field of antitumor. The compound of formula (I) shows degradation and inhibitory effects on BCR-ABL target protein, which is mainly comprised of four moieties, wherein the first moiety (BCR-ABL-TKIs) is compound moiety with BCR-ABL tyrosine kinase inhibited activity; the second moiety (the LIN) is link units; the third moiety (the ULM) is a small molecule ligand for VHL or CRBN proteases with ubiquitination; and the four moiety (the group A) is carbonyl group that covalently binds to BCR-ABL-TKIs and LIN, and the LIN is further covalently bonded to ULM. A series of compounds designed and synthesized by the present disclosure shows extensive pharmacological effective, which function to degrade BCR-ABL protein and inhibit BCR-ABL effective, and can be utilized for treating relevant tumor.

The invention discloses a kit for detecting an ABL tyrosine kinase inhibitor based on an HPLC-MS / MS method and a detection method. The ABL tyrosine kinase inhibitor comprises imatinib, dasatinib, nilotinib, panatinib and flumatinib. The kit comprises the following reagents: a sample treatment solution, a standard substance, a quality control substance, an internal standard solution and a mobile phase, wherein the mobile phase comprises a mobile phase A and a mobile phase B; the mobile phase A is a 0.1% formic acid methanol solution; the mobile phase B is a 2 mmol.L <-1 > ammonium acetate and -0.1% formic acid aqueous solution; according to the invention, the concentration of the ABL tyrosine kinase inhibitor in the blood plasma is quantitatively detected based on an HPLC-MS / MS technology; the detection result is not interfered by common drugs and combined drugs, and the accuracy of quantitative detection of the ABL tyrosine kinase inhibitor is greatly improved; the kit is helpful for improving the detection quality of the ABL tyrosine kinase inhibitor and promoting the standardization and normalization of a detection method, so that the blood concentration of the clinical ABL tyrosine kinase inhibitor can be monitored more quickly, accurately and reliably.

The present invention relates to a method of preventing or treating a pathogen infection comprising administering to a mammal in need thereof an effective amount of an inhibitor of Abl tyrosine kinase.

Provided herein are methods of treating a cancer in a patient comprising administration of an effective amount of a nuclease-resistant polynucleotide that hybridizes to the translation initiation site of a Grb2 nucleic acid in the patient and either a Bcr-Abl tyrosine kinase inhibitor (e.g., dasatinib) or a cytidine analogue (e.g., decitabine or cytarabine). The cancer may be Ph+ and / or Bcr-Abl positive chronic myelogenous leukemia or acute myeloid leukemia or myelodysplastic syndrome.

The present invention relates to a method of treating chronic myelogenous leukemia in a subject comprising administering to the subject a compound, such as N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide, that inhibits the T315I mutation in BCR-ABL tyrosine kinase, or a pharmaceutically acceptable salt thereof. The present invention also relates to a pharmaceutical composition comprising a compound such as N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide, that inhibits the T315I mutation in BCR-ABL tyrosine kinase, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

Compositions and methods for inhibiting the growth of cancer cells are provided. The cancer cells, the growth of which is inhibited, have constitutively active Abl tyrosine kinase activity due to a t(9;22)(q34;q11) translocation which results in expression of a chimeric Bcr-Abl protein which has constitutively active Abl tyrosine kinase activity that is believed to play an important role in leukemogenesis. The compositions include a modified protein kinase C(PKC) which has an Abl tyrosine kinase target motif. The methods involve administering the modified PCK to an individual to inhibit the growth of cancer cells that have Abl tyrosine kinase activity.