29 results about "Phosphoinositide Kinase" patented technology

Disclosed in the present invention is a phosphoinositide 3-kinase allosteric inhibitor for treating a disease related to PI3K regulation. Specifically, provided is a compound as represented by formula I or a pharmaceutically acceptable salt thereof. The phosphoinositide 3-kinase allosteric inhibitor of the present invention can effectively conduct allosteric targeted inhibition on a PI3Kα mutation, in particular, a PI3KαH1047R mutation, has relatively good selectivity, and is expected to treat and / or prevent related diseases or disorders.

Aspects disclosed herein relate to compositions comprising novel phosphoinositide 3-kinase (PI3K) inhibitors, and methods of making the novel PI3K inhibitors. Further, various aspects relate to one or more methods of treating a disease using the compositions disclosed herein, including targeted delivery of the novel PI3K inhibitors disclosed herein.

The present invention relates to chemical compounds useful as inhibitors of class II phosphoinositide 3-kinase (PI3K) signaling. The invention further relates to the medical use of inhibitors of class II phosphoinositide 3-kinase (PI3K) signaling in the treatment of medical conditions associated with defective and / or pathological class II phosphoinositide 3-kinase (PI3K) signaling, such as stroke, cardiovascular diseases associated with endothelial cell dysfunction, cancer, cancerometastasis, myopathy and diabetes.

The invention relates to the technical field of biomedicine detection, and discloses a tumor cell marker detection system for predicting the activation state of intracellular protein kinase. Comprising a marker detection module used for qualitatively detecting epithelial cell markers, mesenchymal cell markers, cell polarity markers and extracellular matrix related markers in tumor cells; the data processing module is used for performing cross validation on an epithelial cell marker, a mesenchymal cell marker, a cell polarity marker and an extracellular matrix related marker; the dynamic weighting module is used for performing dynamic weighting on different markers based on a complex system theory, and endowing epithelial cadherin with a higher weight; and the judgment module is used for determining whether epithelial intercellular substance transformation occurs or not according to the dynamically weighted marker data, and predicting the activation state of intracellular phosphoinositide 3-kinase alpha and the invasiveness of tumor cells based on the determination result of the epithelial intercellular substance transformation.

The instant application relates to deazapurines, thienopyrimidines and furopyrimidines with zinc-binding moiety based derivatives and their use in the treatment of phosphoinositide 3-kinase related diseases and disorders such as cancer. The instant application further relates to the treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

The present invention provides heterocyclylamine derivatives of Formula I:wherein the variables are defined herein, that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.

The present disclosure describes a pharmaceutical combination of an anti-CD19 antibody and a phosphoinositide 3-kinase inhibitor for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia.

The present disclosure relates to the use of phosphoinositide 3-kinase (PI3K) inhibitors targeting allosteric and normal pockets of PI3K in methods of treating, preventing, or ameliorating diseases or conditions in which PI3K functions (or in use in treating, preventing, or ameliorating diseases or conditions). The PI3K inhibitors can be used in combination and can target allosteric or normal pockets of PI3K alpha simultaneously, separately, or sequentially. In some aspects of the disclosed methods, PI3K [alpha] inhibitors may target an allosteric or normal pocket of a PI3K [alpha] mutant that is resistant to treatment with another PI3K [alpha] inhibitor that targets a different pocket of PI3K [alpha].

The disclosure relates to adoptive cell therapy compositions including a population of isolated immune cells that are obtained from a donor subject. The immune cells can be modified to suppress Bruton's tyrosine kinase (BTK), interleukin-2-inducible T cell kinase (ITK), delta isoform of phosphoinositide 3-kinase (PI3Kδ), helios, blimp1, SOCS1, GATA3, IL-10, STAT3, TOX, CD25, foxp3, Ezh2, TGF-beta Receptor II, LAG-3, PD-1, TNF-alpha, or combinations thereof. The immune cells are optionally depleted of CD8+ T cells by about 10-fold or greater relative to un-depleted leukocytes.

This application relates to antibodies or antigen-binding fragments thereof that bind to phosphoinositide-3 -kinase interacting protein 1 (PIK3IP1) protein or antigen-binding fragments, as well as polynucleotides and vectors that encode for such antibodies or antigen-binding fragments. This application further relates to methods of producing the antibodies or antigen- binding fragments and using the antibodies or antigen-binding fragments for treatment of diseases.

The present invention relates to an alkyne derivative, a preparation method for same, and applications thereof in medicine. Specifically, the present invention relates to the alkyne derivative as represented by formula (I), the preparation method for same, a pharmaceutically acceptable salt thereof, and uses of them as a therapeutic agent, specifically as a phosphoinositide 3-kinase γ (PI3Kγ) inhibitor, where the definitions of the substituents in formula (I) are identical to the definitions in the description.

Disclosed herein are methods of treating glioblastoma in a subject comprising, among others, administration of sub-maximal tolerance doses and / or intermittent doses of phosphoinositide 3-kinase (PI3K) inhibitors, autophagy inhibitors and / or checkpoint inhibitors.

The invention discloses a phosphoinositide 3-kinase allosteric inhibitor for treating diseases related to PI3K (phosphoinositide 3-kinase) regulation, and particularly provides a compound shown as a formula I or a pharmaceutically acceptable salt thereof. The phosphoinositide 3-kinase allosteric inhibitor can effectively inhibit PI3K alpha mutation, especially PI3K alpha H1047R mutation in an allosteric targeting mode, has good selectivity and is expected to treat and / or prevent related diseases or obstacles.

Compounds of the following formula:having defined substituents. The compounds can inhibit class II phosphoinositide 3-kinase (PI3K) signaling and are useful for the treatment of a medical condition associated with defective PI3K signaling, such as myopathy, cancer, diabetes, thrombosis or cardiovascular disease.

Described herein are benzoxazepin oxazolidinone compounds with phosphoinositide-3 kinase (PI3K) modulation activity or function having the Formula I structure:or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such PI3K modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon PI3K dysregulation.

The invention refers to the field of neurodegenerative diseases including Alzheimer's Disease and a treatment thereof with a Benzoxazepine compound. Benzoxazepine compounds are e.g. known in the treatment of breast cancer and according to the use of the invention are a first therapeutic and prophylactic treatment for neurodegenerative diseases, including Alzheimer's Disease. The invention further relates to test systems for identifying, mapping, elaborating and evaluating said and further therapeutic and prophylactic uses of compounds of interest and / or other pharmaceutical compositions for the treatment of neurodegenerative diseases, including Alzheimer's Disease. (AD)

The disclosure relates to the compound (( R)-3-(6-chloro-3-((l-(2- cyclopropyl-6-fluoro-3-methyl-4-oxo-4H-chromen-8-yl)ethyl)amino) pyridin-2-yl)-l,2,4-oxadiazol-5(4H)-one) of the Formula I, or to a pharmaceutically acceptable salt thereof, which is useful in the treatment of diseases or disorders associated with modulation of PI3K (phosphoinositide 3 kinase), such as e.g. cancer.

The present disclosure relates to compounds of Formula (I) or a prodrug, solvate, enantiomer, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, useful for treating diseases or disorders associated with PI3K modulation as allosteric chromenone inhibitors of phosphoinositide 3-kinases (PI3K), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, W, X, Y, s, and ring A are as described herein.

The present invention relates to salts and crystalline forms of 2-(3-(8-amino-6-(trifluoromethyl) imidazo [1, 2-a] pyrazin-3-yl)-4-methylphenyl)-3, 3, 3-trifluoro-2-hydroxypropanamide, 8-amino-N-(2-hydroxy-2-methylpropyl)-3-(2-methyl-5-(1, 1, 1-trifluoro-2-hydroxypropan-2-yl) phenyl) imidazo [1, 2-a] pyrazin-3-yl)-4-methylphenyl)-3, 3, 3-trifluoro-2-hydroxypropanamide, and a preparation method thereof. The present invention relates to crystalline forms of 8-amino-N-(2-hydroxy-2-methylpropyl)-3-(2-(methyl-d3)-5-(1, 1, 1-trifluoro-2-hydroxypropyl-2-yl) phenyl) imidazo [1, 2-a] pyrazine-6-carboxamide, which are PI3K inhibitors useful in the treatment of cancer and other diseases, as well as crystalline forms of 8-amino-N-(2-hydroxy-2-methylpropyl)-3-(2-(methyl-d3)-5-(1, 1, 1-trifluoro-2-hydroxypropyl-2-yl) phenyl) imidazo [1, 2-a] pyrazine-6-carboxamide.

Provided are compositions comprising (i) a hydrogen sulfide donor compound, a chalcogenide, or a sulfide salt and (ii) a dual inhibitor of mammalian target of rapamycin (mTOR) and phosphoinositide 3-kinase (PI3K) or a combination of an mTOR inhibitor and a PI3K inhibitor. Also provided are methods for inducing a state of stasis in cells, tissues, or organs with applications to the storage and preservation of biological materials as well as transplantation of biological materials.

Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and / or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

The present application describes benzoxazepine oxazolidinone compounds having phosphoinositide-3-kinase (PI3K) regulating activity or function and stereoisomers, tautomers or pharmaceutically acceptable salts thereof, wherein the compound is selected from the following formula I structure and has substituents and structural features described in the present application. The present application also describes pharmaceutical compositions and drugs comprising compounds of formula I, as well as methods for using such PI3K regulators alone and in combination with other therapeutic agents to treat diseases or conditions mediated or dependent on PI3K disorders.

Described herein are benzoxazepin oxazolidinone compounds with phosphoinositide-3 kinase (PI3K) modulation activity or function having the Formula I structure:or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such PI3K modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon PI3K dysregulation.

The present disclosure relates to the use of phosphoinositide 3-kinase (PI3K) inhibitors targeting allosteric and normal pockets of PI3K in methods of treating, preventing, or ameliorating diseases or conditions in which PI3K functions (or in use in treating, preventing, or ameliorating diseases or conditions). The PI3K inhibitors can be used in combination and can target allosteric or normal pockets of PI3K alpha simultaneously, separately, or sequentially. In some aspects of the disclosed methods, PI3K [alpha] inhibitors may target an allosteric or normal pocket of a PI3K [alpha] mutant that is resistant to treatment with another PI3K [alpha] inhibitor that targets a different pocket of PI3K [alpha].

Provided herein are compounds of formula (I) that modulate PlKfyve and methods of using the compounds in PlKfyve-associated disorders, such as fibro-inflammatory conditions (e.g., interstitial lung disease, or a liver, kidney, cardiac, or systemic fibrotic condition).

The invention discloses a PI3K allosteric inhibitor and application thereof. The present invention provides a compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. The phosphoinositide 3-kinase allosteric inhibitor disclosed by the invention can effectively inhibit PI3K alpha mutation in an allosteric targeting manner, particularly PI3K alpha H1047R mutation and PI3K alpha E545K mutation, has relatively good selectivity, and is expected to treat related diseases or obstacles. # imgabs0 #

Methods and compositions for treating, inhibiting, and / or preventing diseases or disorders associated with aberrant bromodomain-containing protein 4 (BRD4) and phosphoinositide 3-kinase (PBK) activity are disclosed, the methods comprise contacting a solution, cell, tissue, or subject expressing BRD4 and PBK with a compound having Benzopyran-4-One core.

The present intention relates to compound comprising the general structure P-L-J-E, wherein P is a phosphoinositide 3-kinase (PI3K) binding moiety that binds class 1 phosphoinositide 3-kinase (PI3K), L is a linker with a linker length of 12 to 21 atoms, J is a junction selected from (formula I), (formula II) and (formula III), wherein R7 is selected from H and the group consisting of -C1-C3 alkyl; E is an E3 ubiquitin ligase binding moiety that binds cereblon, J is a junction selected from (formula IV), (formula I), (formula II) and (formula III), R7 is selected from H and the group consisting of -C1-C3 alkyl; and SP is chosen in such way that the length of the linker L is 12 to 21 atoms.

Application of a central small molecule protein ILF3 in the preparation of antihypertensive drugs. Essential hypertension is characterized by overactive sympathetic nerves and is closely related to the abnormal excitation of presympathetic neurons in the rostral ventrolateral medulla. Interleukin enhancer-binding factor 3 (ILF3) has multiple biological functions, such as promoting RNA synthesis, transfer, and stability. Moreover, ILF3 is expressed in blood vessels, the heart, and the central nervous system and plays an important role in maintaining normal cardiovascular function. In addition, the phosphatidylinositol 3-kinase / protein kinase B signaling pathway is involved in the regulation of the activities of various tissue cells. Therefore, by studying the role of ILF3 in the regulation of carbon monoxide production in hypertension in the RVLM, the present invention provides a feasible theoretical basis and method for treating hypertension by targeting the central small molecule protein ILF3, aiming to solve the problems of poor compliance of long-term drug treatment for the existing prevention and treatment of hypertension and high drug treatment costs.