60 results about "Phosphoinositide Kinase" patented technology

The invention relates generally to methods for treating and / or preventing aberrant proliferation of hematopoietic cells. More particularly, the invention relates to methods for treating and / or preventing aberrant proliferation of hematopoietic cells comprising selectively inhibiting phosphoinositide 3-kinase delta (PI3Kδ) activity in hematopoietic cells. The methods may be used to treat any indication involving aberrant proliferation of hematopoietic cells.

The invention relates generally to methods for inhibiting angiogenesis. More particularly, methods for inhibiting angiogenesis comprise selectively inhibiting phosphoinositide 3-kinase delta (PI3Kδ) activity in endothelial cells. The methods may comprise administration of one or more cytotoxic therapies including but not limited to radiation, chemotherapeutic agents, photodynamic therapies, radiofrequency ablation, anti-angiogenic agents, and combinations thereof.

The present invention relates to selective inhibitors of phosphoinositide (PI) 3-kinase β, use of the selective inhibitors in anti-thrombotic therapy, and a method for screening compounds useful for the new anti-thrombotic therapy by detecting selective inhibitory activity of PI 3-kinase β of the compound. The invention also relates to novel compounds that are inhibitors of PI 3-kinase.

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 the treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

The invention discloses a phosphoinositide 3-kinase (P13K) inhibitor, a pharmaceutical composition containing the P13K inhibitor, and application of the P13K inhibitor and the pharmaceutical composition. The P13K inhibitor comprises a pyrimidine compound and a stereoisomer / hydrate / pharmaceutically-acceptable salt thereof. The pyrimidine compound has a general formula I of which the structure is shown in the specification. The P13K inhibitor and the pharmaceutical composition containing the same can be used for inhibiting PI3 Ks and treating proliferative diseases on which the PI3 Ks act. According to the invention, high-effectiveness and high-selectivity inhibitors for treating proliferative diseases on which PI3Ks act can be provided.

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 provides a compound of Formula I,Pharmaceutical compositions comprising such compounds and the use of such compounds 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 invention relates to new triazines (G=Q=U are N), pyrimidines (two out of G, Q and U are N), and pyridopyrimidines (one of G and U together with R2 forms an anullated pyridine ring) of formula (I) carrying a spirocyclic substituent, wherein E1 is CR4 or N; X1 is CHR4, CH2CH2, NR4, NR4→0, or O; and the other substituents are as defined in the specification. The compounds inhibit phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), DNA-PK and ATM kinase, and may be used as therapeutic agents or diagnostic probes. The invention also relates to methods of using the compounds for treatment of associated pathological conditions.

The present invention relates to pyridine methylene azolidinone compounds of Formula (I)for the treatment and / or prophylaxis of autoimmune disorders and / or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, allergy, asthma, pancreatitis, multi-organ failure, kidney diseases, platelet aggregation, cancer, sperm motility, graft rejection or lung injuries. Specifically, the present invention is related to pyridine methylene azolidinone derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide-3-kinases, PI3Ks.

The invention provides an anti-cancer sustained-release agent co-carrying glucocorticoid and chemotherapeutic drugs and belongs to sustained-release injections. The anti-cancer sustained-release agent comprises sustained-release microspheres and a solvent, wherein, the sustained-release microspheres comprise anti-cancer active components and sustained-release auxiliary materials; and the solvent is a particular solvent containing a suspending agent. The glucocorticoid is selected from prednisolone, methylprednisolone, dexamethasone, betemethasone, triamcinolone acetonide or triamcinolone acetonide; the chemotherapeutic drugs are selected from phosphoinositide 3-kinase inhibitor, pyrimidine analogues and the like; the sustained-release auxiliary materials are biocompatible high-polymers, such as polylactic acid and the copolymers thereof, polyethylene glycol, carboxyl-terminated polylactic acid copolymers, polyfatty acid dimer-sebacic acid copolymers, poly(erucic acid dimer-sebacic acid), poly(fumaric-co-sebacic acid), polifeprosan and the like; and the suspending agent with the viscosity being 100cp to 3,000cp (at the temperature of 20 to 30 DEG C) is selected from sodium carboxymethyl cellulose and the like. The anti-cancer active components and the sustained-release microspheres can further be prepared into sustained-release implants which can effectively inhibit the growth of tumors, alleviate edema and improve the curative effects of radiotherapy and chemotherapy by intra-tumor or peri-tumor injection or placement.

The invention provides a compound of Formula I,Pharmaceutical compositions comprising such compounds and the use of such compounds 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.

Disclosed is a compound anticancer slow release agent which comprises slow release microspheres and dissolvent, wherein the slow release microballoons comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being specific dissolvent containing suspension adjuvant. The anticancer effective ingredients include Aclarubicin, Idarubicin, Doxorubicin, Epirubicin, Valtaxin, Pirarubicin, Losaxantrone, Losoxantrone and / or anticancer antibiotic synergistic agents selected from phosphoinositide-3-kinase inhibitor, pyrimidine analogues and / or DNA restoration enzyme inhibitor, the slow release auxiliary materials are selected from polylactic acid copolymer EVAc, or sebacic acid copolymer, the viscosity of the suspension adjuvant is 100-3000cp (at 20-30 deg C). The slow release microspheres can also be prepared into slow release implanting agent for lowering down the whole body toxicity reaction of the medicament when locally dispensing on the tumor, and for selectively increasing the tumor local medicinal concentration.

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.

A slow-release anticancer injection contains the slow-release microspheres and solvent. Said slow-release microsphere contains the active anticancer component chosen from 16 vascula inhibitors including gefitinib, angiostatin, etc and 3 cytotoxins including phosphoinositide 3-kinase inhibitor, pyrimidine analog or DNA repairase inhibitor, and the slow-release auxiliary.

A slow-release anticancer injection contains the slow-release microspheres and solvent. Said slow-release microsphere contains the active anticancer component chosen from 6 Pt compounds including bicycloplatinum, etc and 3 cytotoxins including phosphoinositide 3-kinase inhibitor, pyrimidine analog or DNA repairase inhibitor, and the slow-release auxiliary.

A slow-release anticancer injection contains the slow-release microspheres and solvent. Said slow-release microsphere contains the active anticancer component chosen from 13 antimetabolic medicines including gemcitabine, zalcitabine, etc and 3 cytotoxins including phosphoinositide 3-kinase inhibitor, pyrimidine analog or DNA repairase inhibitor, and the slow-release auxiliary.

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 invention is directed to a dual inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC), including a core containing a quinazoline moiety or a quinazolin-4(3H)-one moiety, a kinase hinge binding moiety, and a histone deacetylase pharmacophore, a pharmaceutically acceptable salt thereof, a prodrug thereof, or solvate thereof. The present invention is also directed to a histone deacetylase inhibitor, including a core containing a quinazolin-4(3H)-one moiety and a histone deacetylase pharmacophore.

The invention discloses a phosphoinositide 3-kinase EST segment in common wild rice expressed by bacterial blight stress. The nucleotide sequence of the EST segment is disclosed as SEQ ID NO:1. The invention provides the EST segment for the first time, and the EST directly participates in the anti-disease response process of common wild rice and is a gene directly related to bacterial blight resistance. The EST segment provides partial sequence information for separating and cloning the gene full-length cDNA sequence, and provides theoretical references for researching bacterial blight resistance mechanism of the phosphoinositide 3-kinase in common wild rice. The primer designed by using the EST segment can detection the expression condition of the EST segment by bacterial blight stress in common wild rice leaves, thereby obtaining the expression spectrum of the gene after expression by bacterial blight stress in common wild rice, and laying the foundation for recognizing the functions of the gene and deeply researching the bacterial blight resistance mechanism of the gene in common wild rice.

The slow released injection containing taxane and its synergist consists of slow released microballoon and solvent. The slow released microballoon includes effective anticancer component and slow releasing supplementary material, and the solvent is common solvent or special solvent containing suspending agent. The effective anticancer component is taxane and / or taxane synergist of phosphorinositide 3-kinase inhibitor, pyrimidine analogue and / or DNA repair enzyme inhibitor; the slow releasing supplementary material is PLA, PLGA, EVAc, etc or their composition; and the suspending agent is sodium carboxymethyl cellulose, etc. The slow released microballoon may be also prepared into implantation preparation. Implanting or injecting the slow released preparation to local tumor part can lower the systematic toxic reaction of the medicine and raise the medicine concentration of local tumor part selectively to raise the treating effect.

The invention provides a grape polyphosphoinositide kinase gene VvIPK2 with a sequence of SEQ ID NO:1 in a sequence table and also provides grape polyphosphoinositide kinase with an amino acid sequence of SEQ ID NO:2. In the invention, the polyphosphoinositide kinase gene VvIPK2 of a test tube seedling of a wine grape rootstock variety 'F-242' is cloned, and tests prove that grape blades VvIPK2 participate in a grape cold resisting process and the gene VvIPK2 is transferred to arabidopsis, therefore, the invention provides a theoretical basis for improving the grape resistance by using a transgenic technology. According to the invention, H2O2 is proved to be positioned on the upstream of the VvIPK2 to play a role; and the grape polyphosphoinositide kinase gene VvIPK2 has important guiding significance in researching influence of two signal elements on gene expression with cold regulation, change of transcriptome and change of protein level by means of molecular biology, information biology and proteomics, and deeply researching a plant-influenced low-temperature forced signal transduction mechanism.

Disclosed is an anticancer slow release injection carrying both blood vessel inhibiting agent and its synergistic agent, which comprises slow release microspheres and dissolvent, wherein the slow release microballoons comprise anti-cancer active constituents and slow release auxiliary materials, the dissolvent being specific dissolvent containing suspension adjuvant. The anti-cancer active constituents include blood vessel inhibiting agent selected from gefinitib, erlotinib, lapatinib, angiostatin, endostatin, imatinib, sorafenib, sunitinib, Toaosta, Panitoma and / or cytotoxic drugs selected from phosphoinositide 3-enzyme inhibitor, pyrimidine analog and / or DNA restoring enzyme inhibitor, the slow release auxiliary materials include biocompatible high polymers, the viscosity of the suspension adjuvant is 100-3000cp (at 20-30 deg C), and is selected from sodium carboxymethylcellulose.

A anti-cancer slow-release agent co-loaded with glucocorticosteroid and chemotherapy medicament is a slow-release injection agent composed of slow-release microsphere and solvent, wherein, the slow-release microsphere comprises anti-cancer effective ingredient and slow-release auxiliary materials, the solvent is the special solvent containing suspending agent. The glucocorticosteroid is selected from prednisolone, methylprednisolone, dexamethasone, betamethasone, omcilon or triamcinoloneAcetonide, the chemotherapy medicament is selected from phosphoinositide 3-kinase restrainer and pyrimidine analogue or the like; the slow-release auxiliary materials are polylactic acid and copolymer thereof, polyethyleneglycol, polylactide-COOH copolymer, 2-aliphatic acid, sebacic acid polyester, poly(erucic acid dimmer-sebacic acid), poly(fumaric acid-sebacic acid), polyphenyl and polylactic acid or the like biocompatibility high molecules; the suspending agent viscosity is 100cp-3000cp (20 DEG C-30DEG C) and the suspending agent is selected from sodium carboxymethyl cellulose. The anti-cancer effective compositin and the slow-release microsphere can be made into a slow-release implantation agent, by intra-tumor injection or tumor circumference injection or arrangement, the tumor growth can be effectively inhibited, the edema can be alleviated, and the curative effects of the chemotherapy and the radiation therapy can be reinforced.

Morpholino-substituted pyridopyrimidine, quinolone, and benzopyranone derivatives inhibit phosphoinositide (PI) 3-kinase, an enzyme that regulates platelet-adhesion processes. As a consequence, the compounds in question have anti-thrombotic activity, as well as other pharmaceutical properties. The compounds claimed are represented by formula (I), (II) and (III). PI 3-kinase generates 3-phosphorylated PI second messengers which stimulate platelet adhesion under blood-flow conditions. Because platelet adhesion is a necessary step in the formation of a thrombus, inhibition by these compounds of PI 3-kinase under such conditions inhibits or prevents thrombus formation. The compounds are useful in treating PI 3-kinase-dependent conditions including cardiovascular diseases such as coronary artery occlusion, stroke, acute coronary syndrome, acute myocardial infarction, vascular restenosis, atherosclerosis, and unstable angina; respiratory diseases such as asthma, chronic obstructive pulmonary diseases (COPD), and bronchitis; inflammatory disorders, neoplasms including cancers such as glioma, prostate cancer, small cell lung cancer, and breast cancer, and diseases linked to disordered white blood cell function, such as autoimmune and inflammatory diseases.

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 cyclin-dependent kinase-4 / 6 (CDK4 / 6) inhibitor, and / or a Bruton's tyrosine kinase (BTK) inhibitor are described. In certain embodiments, the invention includes therapeutic combinations of a cyclin-dependent kinase-4 / 6 (CDK4 / 6) inhibitor and a BTK inhibitor, a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a JAK-2, PI3K-δ, and BTK inhibitor.

The present invention is related to quinoxaline compounds of Formula (I) in particular for the treatment of autoimmune disorders and / or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, transplantation, graft rejection or lung injuries.

The invention relates to novel phosphoinositide 3-kinase (PI3k), mammalian target of rapamycin (mTOR) and PI3k-related kinase (PIKKs) inhibitor compounds of formula (I),wherein X1, X2 and X3 are N or CH, with the proviso that at least two of X1, X2 and X3 are N; Y is N or CH, These compounds are useful, either alone or in combination with further therapeutic agents, for treating disorders mediated by lipid kinases.

The present invention is directed to compounds and pharmaceutically acceptable salts thereof which are inhibitors of the activity or function of the phosphoinositide 3'OH kinase family (hereinafter PI3K) for use in the treatment or prevention of respiratory infections, the treatment of airway damage, and / or the prevention of airway injury in patients with a PI3K Delta mutation.